Input: What are the genetic changes related to very long-chain acyl-CoA dehydrogenase deficiency ?

Output: Mutations in the ACADVL gene cause VLCAD deficiency. This gene provides instructions for making an enzyme called very long-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called very long-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.  Mutations in the ACADVL gene lead to a shortage (deficiency) of the VLCAD enzyme within cells. Without sufficient amounts of this enzyme, very long-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to the characteristic signs and symptoms of this disorder such as lethargy and hypoglycemia. Very long-chain fatty acids or partially metabolized fatty acids may also build up in tissues and damage the heart, liver, and muscles. This abnormal buildup causes the other signs and symptoms of VLCAD deficiency. </s>


Input: Is very long-chain acyl-CoA dehydrogenase deficiency inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for very long-chain acyl-CoA dehydrogenase deficiency ?

Output: These resources address the diagnosis or management of VLCAD deficiency:  - Baby's First Test  - Gene Review: Gene Review: Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency  - Genetic Testing Registry: Very long chain acyl-CoA dehydrogenase deficiency  - MedlinePlus Encyclopedia: Newborn Screening Tests   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) familial HDL deficiency ?

Output: Familial HDL deficiency is a condition characterized by low levels of high-density lipoprotein (HDL) in the blood. HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. People with familial HDL deficiency may develop cardiovascular disease at a relatively young age, often before age 50.  Severely reduced levels of HDL in the blood is a characteristic feature of a related disorder called Tangier disease. People with Tangier disease have additional signs and symptoms, such as disturbances in nerve function; enlarged, orange-colored tonsils; and clouding of the clear covering of the eye (corneal clouding). However, people with familial HDL deficiency do not have these additional features. </s>


Input: How many people are affected by familial HDL deficiency ?

Output: Familial HDL deficiency is a rare disorder, although the prevalence is unknown. </s>


Input: What are the genetic changes related to familial HDL deficiency ?

Output: Mutations in the ABCA1 gene or the APOA1 gene cause familial HDL deficiency. The proteins produced from these genes work together to remove cholesterol and phospholipids from cells.  The ABCA1 gene provides instructions for making a protein that removes cholesterol and phospholipids from cells by moving them across the cell membrane. The movement of these substances across the membrane is enhanced by another protein called apolipoprotein A-I (apoA-I), which is produced by the APOA1 gene. Once outside the cell, the cholesterol and phospholipids combine with apoA-I to form HDL. ApoA-I also triggers a reaction that converts cholesterol to a form that can be fully integrated into HDL and transported through the bloodstream.  ABCA1 gene mutations and some APOA1 gene mutations prevent the release of cholesterol and phospholipids from cells. Other mutations in the APOA1 gene reduce the protein's ability to stimulate the conversion of cholesterol. These ABCA1 and APOA1 gene mutations decrease the amount of cholesterol or phospholipids available to form HDL, resulting in low levels of HDL in the blood. A shortage (deficiency) of HDL is believed to increase the risk of cardiovascular disease. </s>


Input: Is familial HDL deficiency inherited ?

Output: Familial HDL deficiency is inherited in an autosomal dominant pattern, which means an alteration in one copy of either the ABCA1 or the APOA1 gene in each cell is sufficient to cause the disorder. People with alterations in both copies of the ABCA1 gene develop the related disorder Tangier disease. </s>


Input: What are the treatments for familial HDL deficiency ?

Output: These resources address the diagnosis or management of familial HDL deficiency:  - Genetic Testing Registry: Familial hypoalphalipoproteinemia   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?

Output: The combination of intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies is commonly known by the acronym IMAGe. This rare syndrome has signs and symptoms that affect many parts of the body.  Most affected individuals grow slowly before birth (intrauterine growth restriction) and are small in infancy. They have skeletal abnormalities that often become apparent in early childhood, although these abnormalities are usually mild and can be difficult to recognize on x-rays. The most common bone changes are metaphyseal dysplasia and epiphyseal dysplasia; these are malformations of the ends of long bones in the arms and legs. Some affected individuals also have an abnormal side-to-side curvature of the spine (scoliosis) or thinning of the bones (osteoporosis).  Adrenal hypoplasia congenita is the most severe feature of IMAGe syndrome. The adrenal glands are a pair of small glands on top of each kidney. They produce a variety of hormones that regulate many essential functions in the body. Underdevelopment (hypoplasia) of these glands prevents them from producing enough hormones, a condition known as adrenal insufficiency. The signs of adrenal insufficiency begin shortly after birth and include vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), and shock. If untreated, these complications can be life-threatening.  The genital abnormalities associated with IMAGe syndrome occur only in affected males. They include an unusually small penis (micropenis), undescended testes (cryptorchidism), and the opening of the urethra on the underside of the penis (hypospadias).  Several additional signs and symptoms have been reported in people with IMAGe syndrome. Some affected individuals have distinctive facial features, such as a prominent forehead, low-set ears, and a short nose with a flat nasal bridge. Less commonly, people with this condition have premature fusion of certain bones of the skull (craniosynostosis), a split in the soft flap of tissue that hangs from the back of the mouth (cleft or bifid uvula), a high-arched roof of the mouth (palate), and a small chin (micrognathia). Other possible features of IMAGe syndrome include high levels of calcium in the blood (hypercalcemia) or urine (hypercalcuria) and a shortage of growth hormone in childhood that results in short stature. </s>


Input: How many people are affected by intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?

Output: IMAGe syndrome is very rare, with only about 20 cases reported in the medical literature. The condition has been diagnosed more often in males than in females, probably because females do not have associated genital abnormalities. </s>


Input: What are the genetic changes related to intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?

Output: IMAGe syndrome is caused by mutations in the CDKN1C gene. This gene provides instructions for making a protein that helps control growth before birth. The mutations that cause IMAGe syndrome alter the structure and function of the CDKN1C protein, which inhibits normal growth starting in the early stages of development before birth. Researchers are working to determine how these genetic changes underlie the bone abnormalities, adrenal gland underdevelopment, and other signs and symptoms of this condition.  People inherit one copy of most genes from their mother and one copy from their father. For most genes, both copies are fully turned on (active) in cells. The CDKN1C gene, however, is most active when it is inherited from a person's mother. The copy of CDKN1C inherited from a person's father is active at much lower levels in most tissues. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting. When genomic imprinting reduces the activity of the copy of a gene inherited from the father, that gene is said to be paternally imprinted. </s>


Input: Is intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies inherited ?

Output: The inheritance of IMAGe syndrome is complex. The condition is described as having an autosomal dominant inheritance pattern because one copy of the altered CDKN1C gene in each cell is sufficient to cause the disorder. However, because this gene is paternally imprinted, IMAGe syndrome results only when the mutation is present on the maternally inherited copy of the gene. When a mutation affects the paternally inherited copy of the CDKN1C gene, it does not cause health problems. Therefore, IMAGe syndrome is passed only from mothers to their children. </s>


Input: What are the treatments for intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies ?

Output: These resources address the diagnosis or management of IMAGe syndrome:  - Gene Review: Gene Review: IMAGe Syndrome  - Genetic Testing Registry: Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies  - National Institutes of Health Clinical Center: Managing Adrenal Insufficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) distal hereditary motor neuropathy, type II ?

Output: Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement, primarily in the legs.  Onset of distal hereditary motor neuropathy, type II ranges from the teenage years through mid-adulthood. The initial symptoms of the disorder are cramps or weakness in the muscles of the big toe and later, the entire foot. Over a period of approximately 5 to 10 years, affected individuals experience a gradual loss of muscle tissue (atrophy) in the lower legs. They begin to have trouble walking and running, and eventually may have complete paralysis of the lower legs. The thigh muscles may also be affected, although generally this occurs later and is less severe.  Some individuals with distal hereditary motor neuropathy, type II have weakening of the muscles in the hands and forearms. This weakening is less pronounced than in the lower limbs and does not usually result in paralysis. </s>


Input: How many people are affected by distal hereditary motor neuropathy, type II ?

Output: The prevalence of distal hereditary motor neuropathy, type II is unknown. At least 25 affected families have been identified worldwide. </s>


Input: What are the genetic changes related to distal hereditary motor neuropathy, type II ?

Output: Mutations in the HSPB1 and HSPB8 genes cause distal hereditary motor neuropathy, type II. These genes provide instructions for making proteins called heat shock protein beta-1 and heat shock protein beta-8. Heat shock proteins help protect cells under adverse conditions such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. They block signals that lead to programmed cell death. In addition, they appear to be involved in activities such as cell movement (motility), stabilizing the cell's structural framework (the cytoskeleton), folding and stabilizing newly produced proteins, and repairing damaged proteins. Heat shock proteins also appear to play a role in the tensing of muscle fibers (muscle contraction).  Heat shock protein beta-1 and heat shock protein beta-8 are found in cells throughout the body and are abundant in nerve cells. In nerve cells, heat shock protein beta-1 helps to organize a network of molecular threads called neurofilaments that maintain the diameter of specialized extensions called axons. Maintaining proper axon diameter is essential for the efficient transmission of nerve impulses. The function of heat shock protein beta-8 is not well understood, but studies have shown that it interacts with heat shock protein beta-1.  The HSPB1 and HSPB8 gene mutations that cause distal hereditary motor neuropathy, type II change single protein building blocks (amino acids) in the protein sequence. If either protein is altered, they may be more likely to cluster together and form clumps (aggregates). Aggregates of heat shock proteins may block the transport of substances that are essential for the proper function of nerve axons. The disruption of other cell functions in which these proteins are involved may also contribute to the signs and symptoms of distal hereditary motor neuropathy, type II. </s>


Input: Is distal hereditary motor neuropathy, type II inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for distal hereditary motor neuropathy, type II ?

Output: These resources address the diagnosis or management of distal hereditary motor neuropathy, type II:  - Genetic Testing Registry: Distal hereditary motor neuronopathy type 2A  - Genetic Testing Registry: Distal hereditary motor neuronopathy type 2B  - MedlinePlus Encyclopedia: Weakness   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) primary hyperoxaluria ?

Output: Primary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. The condition often results in end stage renal disease (ESRD), which is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.  Primary hyperoxaluria results from the overproduction of a substance called oxalate. Oxalate is filtered through the kidneys and excreted as a waste product in urine, leading to abnormally high levels of this substance in urine (hyperoxaluria). During its excretion, oxalate can combine with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones. Deposits of calcium oxalate can damage the kidneys and other organs and lead to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and injury to other organs. Over time, kidney function decreases such that the kidneys can no longer excrete as much oxalate as they receive. As a result oxalate levels in the blood rise, and the substance gets deposited in tissues throughout the body (systemic oxalosis), particularly in bones and the walls of blood vessels. Oxalosis in bones can cause fractures.  There are three types of primary hyperoxaluria that differ in their severity and genetic cause. In primary hyperoxaluria type 1, kidney stones typically begin to appear anytime from childhood to early adulthood, and ESRD can develop at any age. Primary hyperoxaluria type 2 is similar to type 1, but ESRD develops later in life. In primary hyperoxaluria type 3, affected individuals often develop kidney stones in early childhood, but few cases of this type have been described so additional signs and symptoms of this type are unclear. </s>


Input: How many people are affected by primary hyperoxaluria ?

Output: Primary hyperoxaluria is estimated to affect 1 in 58,000 individuals worldwide. Type 1 is the most common form, accounting for approximately 80 percent of cases. Types 2 and 3 each account for about 10 percent of cases. </s>


Input: What are the genetic changes related to primary hyperoxaluria ?

Output: Mutations in the AGXT, GRHPR, and HOGA1 genes cause primary hyperoxaluria types 1, 2, and 3, respectively. These genes provide instructions for making enzymes that are involved in the breakdown and processing of protein building blocks (amino acids) and other compounds. The enzyme produced from the HOGA1 gene is involved in the breakdown of an amino acid, which results in the formation of a compound called glyoxylate. This compound is further broken down by the enzymes produced from the AGXT and GRHPR genes.  Mutations in the AGXT, GRHPR, or HOGA1 gene lead to a decrease in production or activity of the respective proteins, which prevents the normal breakdown of glyoxylate. AGXT and GRHPR gene mutations result in an accumulation of glyoxylate, which is then converted to oxalate for removal from the body as a waste product. HOGA1 gene mutations also result in excess oxalate, although researchers are unsure as to how this occurs. Oxalate that is not excreted from the body combines with calcium to form calcium oxalate deposits, which can damage the kidneys and other organs. </s>


Input: Is primary hyperoxaluria inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for primary hyperoxaluria ?

Output: These resources address the diagnosis or management of primary hyperoxaluria:  - Gene Review: Gene Review: Primary Hyperoxaluria Type 1  - Gene Review: Gene Review: Primary Hyperoxaluria Type 2  - Gene Review: Gene Review: Primary Hyperoxaluria Type 3  - Genetic Testing Registry: Hyperoxaluria  - Genetic Testing Registry: Primary hyperoxaluria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?

Output: Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. In people with HANAC syndrome, angiopathy affects several parts of the body. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage.  People with HANAC syndrome develop kidney disease (nephropathy). Fragile or damaged blood vessels or basement membranes in the kidneys can lead to blood in the urine (hematuria). Cysts can also form in one or both kidneys, and the cysts may grow larger over time.  Compared to other COL4A1-related disorders, the brain is only mildly affected in HANAC syndrome. People with this condition may have a bulge in one or multiple blood vessels in the brain (intracranial aneurysms). These aneurysms have the potential to burst, causing bleeding within the brain (hemorrhagic stroke). However, in people with HANAC syndrome, these aneurysms typically do not burst. About half of people with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).  Muscle cramps experienced by most people with HANAC syndrome typically begin in early childhood. Any muscle may be affected, and cramps usually last from a few seconds to a few minutes, although in some cases they can last for several hours. Muscle cramps can be spontaneous or triggered by exercise.  Individuals with HANAC syndrome also experience a variety of eye problems. All individuals with this condition have arteries that twist and turn abnormally within the light-sensitive tissue at the back of the eyes (arterial retinal tortuosity). This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. Other eye problems associated with HANAC syndrome include a clouding of the lens of the eye (cataract) and an abnormality called Axenfeld-Rieger anomaly. Axenfeld-Rieger anomaly is associated with various other eye abnormalities, including underdevelopment and eventual tearing of the colored part of the eye (iris), and a pupil that is not in the center of the eye.  Rarely, affected individuals will have a condition called Raynaud phenomenon in which the blood vessels in the fingers and toes temporarily narrow, restricting blood flow to the fingertips and the ends of the toes. As a result, the skin around the affected area may turn white or blue for a brief period of time and the area may tingle or throb. Raynaud phenomenon is typically triggered by changes in temperature and usually causes no long term damage. </s>


Input: How many people are affected by hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?

Output: HANAC syndrome is a rare condition, although the exact prevalence is unknown. At least six affected families have been described in the scientific literature. </s>


Input: What are the genetic changes related to hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?

Output: Mutations in the COL4A1 gene cause HANAC syndrome. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).  The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken. </s>


Input: Is hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome ?

Output: These resources address the diagnosis or management of HANAC syndrome:  - Gene Review: Gene Review: COL4A1-Related Disorders  - Genetic Testing Registry: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) African iron overload ?

Output: African iron overload is a condition that involves absorption of too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the liver, bone marrow, and spleen. Humans cannot increase the excretion of iron, although some iron is lost through bleeding or when cells of the intestine (enterocytes) are shed at the end of the cells' lifespan. Iron levels in the body are primarily regulated through control of how much iron is absorbed from the diet.  African iron overload results from a diet high in iron. It is particularly associated with consumption of a traditional African beer that contains dissolved iron from the metal drums in which it is brewed. Some evidence suggests that a genetic predisposition to absorbing too much iron may also be involved.  In African iron overload, excess iron typically accumulates in liver cells (hepatocytes) and certain immune cells called reticuloendothelial cells. Reticuloendothelial cells include macrophages in the bone marrow and spleen and Kuppfer cells, which are specialized macrophages found in the liver. Kuppfer cells and other macrophages help protect the body against foreign invaders such as viruses and bacteria.  When too much iron is absorbed, the resulting iron overload can eventually damage tissues and organs. Iron overload in the liver may lead to chronic liver disease (cirrhosis) in people with African iron overload. Cirrhosis increases the risk for developing a type of liver cancer called hepatocellular carcinoma. Iron overload in immune cells may affect their ability to fight infections. African iron overload is associated with an increased risk of developing infections such as tuberculosis.  People with African iron overload may have a slightly low number of red blood cells (mild anemia), possibly because the iron that accumulates in the liver, bone marrow, and spleen is less available for production of red blood cells. Affected individuals also have high levels of a protein called ferritin in their blood, which can be detected with a blood test. Ferritin stores and releases iron in cells, and cells produce more ferritin in response to excess amounts of iron. </s>


Input: How many people are affected by African iron overload ?

Output: African iron overload is common in rural areas of central and southern Africa; up to 10 percent of the population in these regions may be affected. Men seem to be affected more often than women, possibly due to some combination of differences in dietary iron consumption and gender differences in the processing of iron.  The prevalence of increased iron stores in people of African descent in other parts of the world is unknown; however, these individuals may be at higher risk of developing mildly increased iron stores than are people of European background. </s>


Input: What are the genetic changes related to African iron overload ?

Output: African iron overload was first noted in rural central and southern African populations among people who drink a traditional beer brewed in uncoated steel drums that allow iron (a component of steel) to leach into the beer. However, not all individuals who drink the beer develop African iron overload, and not all individuals of African descent with iron overload drink the beer. Therefore, researchers are seeking genetic differences that affect the risk of developing this condition.  Some studies have indicated that a variation in the SLC40A1 gene increases the risk of developing increased iron stores in people of African descent. This variation is found in 5 to 20 percent of people of African descent but is not generally found in other populations.  The SLC40A1 gene provides instructions for making a protein called ferroportin. This protein is involved in the process of iron absorption in the body. Iron from the diet is absorbed through the walls of the small intestine. Ferroportin then transports iron from the small intestine into the bloodstream, and the iron is carried by the blood to the tissues and organs of the body. Ferroportin also transports iron out of reticuloendothelial cells in the liver, spleen, and bone marrow. The amount of iron absorbed by the body depends on the amount of iron stored and released from intestinal cells and macrophages.  The SLC40A1 gene variation that some studies have associated with increased iron stores in people of African descent may affect the way ferroportin helps to regulate iron absorption in the body. However, researchers suggest that this variation is not associated with most cases of African iron overload. </s>


Input: Is African iron overload inherited ?

Output: African iron overload seems to run in families, and high iron in a family's diet seems to be the major contributor to development of the condition. There also may be a genetic contribution, but the inheritance pattern is unknown. People with a specific variation in the SLC40A1 gene may inherit an increased risk of this condition, but not the condition itself. Not all people with this condition have the variation in the gene, and not all people with the variation will develop the disorder. </s>


Input: What are the treatments for African iron overload ?

Output: These resources address the diagnosis or management of African iron overload:  - Genetic Testing Registry: African nutritional hemochromatosis   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) hereditary multiple osteochondromas ?

Output: Hereditary multiple osteochondromas is a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. The number of osteochondromas and the bones on which they are located vary greatly among affected individuals. The osteochondromas are not present at birth, but approximately 96 percent of affected people develop multiple osteochondromas by the time they are 12 years old. Osteochondromas typically form at the end of long bones and on flat bones such as the hip and shoulder blade. Once people with hereditary multiple osteochondromas reach adult height and their bones stop growing, the development of new osteochondromas also usually stops.  Multiple osteochondromas can disrupt bone growth and can cause growth disturbances of the arms, hands, and legs, leading to short stature. Often these problems with bone growth do not affect the right and left limb equally, resulting in uneven limb lengths (limb length discrepancy). Bowing of the forearm or ankle and abnormal development of the hip joints (hip dysplasia) caused by osteochondromas can lead to difficulty walking and general discomfort. Multiple osteochondromas may also result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas.  Osteochondromas are typically benign; however, in some instances these tumors become malignant (cancerous). Researchers estimate that people with hereditary multiple osteochondromas have a 1 in 20 to 1 in 200 lifetime risk of developing cancerous osteochondromas (called sarcomas). </s>


Input: How many people are affected by hereditary multiple osteochondromas ?

Output: The incidence of hereditary multiple osteochondromas is estimated to be 1 in 50,000 individuals. This condition occurs more frequently in some isolated populations: the incidence is approximately 1 in 1,000 in the Chamorro population of Guam and 1 in 77 in the Ojibway Indian population of Manitoba, Canada. </s>


Input: What are the genetic changes related to hereditary multiple osteochondromas ?

Output: Mutations in the EXT1 and EXT2 genes cause hereditary multiple osteochondromas. The EXT1 gene and the EXT2 gene provide instructions for producing the proteins exostosin-1 and exostosin-2, respectively. The two exostosin proteins bind together and form a complex found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, the exostosin-1 and exostosin-2 complex modifies a protein called heparan sulfate so it can be used by the cell.  When there is a mutation in exostosin-1 or exostosin-2, heparan sulfate cannot be processed correctly and is nonfunctional. Although heparan sulfate is involved in many bodily processes, it is unclear how the lack of this protein contributes to the development of osteochondromas.  If the condition is caused by a mutation in the EXT1 gene it is called hereditary multiple osteochondromas type 1. A mutation in the EXT2 gene causes hereditary multiple osteochondromas type 2. While both type 1 and type 2 involve multiple osteochondromas, mutations in the EXT1 gene likely account for 55 to 75 percent of all cases of hereditary multiple osteochondromas, and the severity of symptoms associated with osteochondromas seems to be greater in type 1.  Researchers estimate that about 15 percent of people with hereditary multiple osteochondromas have no mutation in either the EXT1 or the EXT2 gene. It is not known why multiple osteochondromas form in these individuals. </s>


Input: Is hereditary multiple osteochondromas inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for hereditary multiple osteochondromas ?

Output: These resources address the diagnosis or management of hereditary multiple osteochondromas:  - Gene Review: Gene Review: Hereditary Multiple Osteochondromas  - Genetic Testing Registry: Multiple congenital exostosis  - Genetic Testing Registry: Multiple exostoses type 2   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Partington syndrome ?

Output: Partington syndrome is a neurological disorder that causes intellectual disability along with a condition called focal dystonia that particularly affects movement of the hands. Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe.  The intellectual disability associated with Partington syndrome usually ranges from mild to moderate. Some affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur in Partington syndrome.  Focal dystonia of the hands is a feature that distinguishes Partington syndrome from other intellectual disability syndromes. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions; tremors; and other uncontrolled movements. The term "focal" refers to a type of dystonia that affects a single part of the body, in this case the hands. In Partington syndrome, focal dystonia of the hands, which is called the Partington sign, begins in early childhood and gradually gets worse. This condition typically causes difficulty with grasping movements or using a pen or pencil.  People with Partington syndrome may also have dystonia affecting other parts of the body; dystonia affecting the muscles in the face and those involved in speech may cause impaired speech (dysarthria). People with this disorder may also have an awkward way of walking (gait). Signs and symptoms can vary widely, even within the same family. </s>


Input: How many people are affected by Partington syndrome ?

Output: The prevalence of Partington syndrome is unknown. About 20 cases have been described in the medical literature. </s>


Input: What are the genetic changes related to Partington syndrome ?

Output: Partington syndrome is caused by mutations in the ARX gene. This gene provides instructions for producing a protein that regulates the activity of other genes. Within the developing brain, the ARX protein is involved with movement (migration) and communication of nerve cells (neurons). In particular, this protein regulates genes that play a role in the migration of specialized neurons (interneurons) to their proper location. Interneurons relay signals between other neurons.  The normal ARX protein contains four regions where a protein building block (amino acid) called alanine is repeated multiple times. These stretches of alanines are known as polyalanine tracts. The most common mutation that causes Partington syndrome, a duplication of genetic material written as c.428_451dup, adds extra alanines to the second polyalanine tract in the ARX protein. This type of mutation is called a polyalanine repeat expansion. The expansion likely impairs ARX protein function and may disrupt normal interneuron migration in the developing brain, leading to the intellectual disability and dystonia characteristic of Partington syndrome. </s>


Input: Is Partington syndrome inherited ?

Output: This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with one altered copy of the gene may have some signs and symptoms related to the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. </s>


Input: What are the treatments for Partington syndrome ?

Output: These resources address the diagnosis or management of Partington syndrome:  - American Academy of Child and Adolescent Psychiatry: Services in School for Children with Special Needs  - American Academy of Pediatrics: What is a Developmental/Behavioral Pediatrician?  - Centers for Disease Control and Prevention: Developmental Screening Fact Sheet  - Genetic Testing Registry: Partington X-linked mental retardation syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) congenital deafness with labyrinthine aplasia, microtia, and microdontia ?

Output: Congenital deafness with labyrinthine aplasia, microtia, and microdontia (also called LAMM syndrome) is a condition that affects development of the ears and teeth. In people with this condition, the structures that form the inner ear are usually completely absent (labyrinthine aplasia). Rarely, affected individuals have some underdeveloped inner ear structures in one or both ears. The abnormalities of the inner ear cause a form of hearing loss called sensorineural deafness that is present from birth (congenital). Because the inner ear is important for balance as well as hearing, development of motor skills, such as sitting and crawling, may be delayed in affected infants. In addition, people with LAMM syndrome often have abnormally small outer ears (microtia) with narrow ear canals. They can also have unusually small, widely spaced teeth (microdontia). </s>


Input: How many people are affected by congenital deafness with labyrinthine aplasia, microtia, and microdontia ?

Output: LAMM syndrome is a rare condition, although its prevalence is unknown. Approximately a dozen affected families have been identified. </s>


Input: What are the genetic changes related to congenital deafness with labyrinthine aplasia, microtia, and microdontia ?

Output: LAMM syndrome is caused by mutations in the FGF3 gene, which provides instructions for making a protein called fibroblast growth factor 3 (FGF3). By attaching to another protein known as a receptor, the FGF3 protein triggers a cascade of chemical reactions inside the cell that signal the cell to undergo certain changes, such as dividing or maturing to take on specialized functions. During development before birth, the signals triggered by the FGF3 protein stimulate cells to form the structures that make up the inner ears. The FGF3 protein is also involved in the development of many other organs and structures, including the outer ears and teeth.  FGF3 gene mutations involved in LAMM syndrome alter the FGF3 protein. The altered protein likely has reduced or absent function and is unable to stimulate signaling. The loss of FGF3 function impairs development of the ears and teeth, which leads to the characteristic features of LAMM syndrome. </s>


Input: Is congenital deafness with labyrinthine aplasia, microtia, and microdontia inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for congenital deafness with labyrinthine aplasia, microtia, and microdontia ?

Output: These resources address the diagnosis or management of LAMM syndrome:  - Gene Review: Gene Review: Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia  - Genetic Testing Registry: Deafness with labyrinthine aplasia microtia and microdontia (LAMM)   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) myosin storage myopathy ?

Output: Myosin storage myopathy is a condition that causes muscle weakness (myopathy) that does not worsen or worsens very slowly over time. This condition is characterized by the formation of protein clumps, which contain a protein called myosin, within certain muscle fibers. The signs and symptoms of myosin storage myopathy usually become noticeable in childhood, although they can occur later. Because of muscle weakness, affected individuals may start walking later than usual and have a waddling gait, trouble climbing stairs, and difficulty lifting the arms above shoulder level. Muscle weakness also causes some affected individuals to have trouble breathing. </s>


Input: How many people are affected by myosin storage myopathy ?

Output: Myosin storage myopathy is a rare condition. Its prevalence is unknown. </s>


Input: What are the genetic changes related to myosin storage myopathy ?

Output: Mutations in the MYH7 gene cause myosin storage myopathy. The MYH7 gene provides instructions for making a protein known as the cardiac beta ()-myosin heavy chain. This protein is found in heart (cardiac) muscle and in type I skeletal muscle fibers, one of two types of fibers that make up the muscles that the body uses for movement. Cardiac -myosin heavy chain is the major component of the thick filament in muscle cell structures called sarcomeres. Sarcomeres, which are made up of thick and thin filaments, are the basic units of muscle contraction. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract.  Mutations in the MYH7 gene lead to the production of an altered cardiac -myosin heavy chain protein, which is thought to be less able to form thick filaments. The altered proteins accumulate in type I skeletal muscle fibers, forming the protein clumps characteristic of the disorder. It is unclear how these changes lead to muscle weakness in people with myosin storage myopathy. </s>


Input: Is myosin storage myopathy inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for myosin storage myopathy ?

Output: These resources address the diagnosis or management of myosin storage myopathy:  - Genetic Testing Registry: Myosin storage myopathy   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) citrullinemia ?

Output: Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes.  Type I citrullinemia (also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems are life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, partial loss of vision, problems with balance and muscle coordination (ataxia), and lethargy. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.  Type II citrullinemia chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. In some cases, the signs and symptoms of this disorder appear during adulthood (adult-onset). These signs and symptoms can be life-threatening, and are known to be triggered by certain medications, infections, surgery, and alcohol intake in people with adult-onset type II citrullinemia.  The features of adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms of NICCD resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult-onset type II citrullinemia. </s>


Input: How many people are affected by citrullinemia ?

Output: Type I citrullinemia is the most common form of the disorder, affecting about 1 in 57,000 people worldwide. Type II citrullinemia is found primarily in the Japanese population, where it occurs in an estimated 1 in 100,000 to 230,000 individuals. Type II also has been reported in other populations, including people from East Asia and the Middle East. </s>


Input: What are the genetic changes related to citrullinemia ?

Output: Mutations in the ASS1 and SLC25A13 genes cause citrullinemia.  Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions that takes place in liver cells. These reactions process excess nitrogen that is generated when protein is used by the body. The excess nitrogen is used to make a compound called urea, which is excreted in urine.  Mutations in the ASS1 gene cause type I citrullinemia. This gene provides instructions for making an enzyme, argininosuccinate synthase 1, that is responsible for one step of the urea cycle. Mutations in the ASS1 gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen (in the form of ammonia) and other byproducts of the urea cycle accumulate in the bloodstream. Ammonia is particularly toxic to the nervous system, which helps explain the neurologic symptoms (such as lethargy, seizures, and ataxia) that are often seen in type I citrullinemia.  Mutations in the SLC25A13 gene are responsible for adult-onset type II citrullinemia and NICCD. This gene provides instructions for making a protein called citrin. Within cells, citrin helps transport molecules used in the production and breakdown of simple sugars, the production of proteins, and the urea cycle. Molecules transported by citrin are also involved in making nucleotides, which are the building blocks of DNA and its chemical cousin, RNA. Mutations in the SLC25A13 gene typically prevent cells from making any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the signs and symptoms of adult-onset type II citrullinemia. A lack of citrin also leads to the features of NICCD, although ammonia does not build up in the bloodstream of infants with this condition. </s>


Input: Is citrullinemia inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for citrullinemia ?

Output: These resources address the diagnosis or management of citrullinemia:  - Baby's First Test: Citrullinemia, Type I  - Baby's First Test: Citrullinemia, Type II  - Gene Review: Gene Review: Citrin Deficiency  - Gene Review: Gene Review: Citrullinemia Type I  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Citrullinemia type I  - Genetic Testing Registry: Citrullinemia type II  - Genetic Testing Registry: Neonatal intrahepatic cholestasis caused by citrin deficiency  - MedlinePlus Encyclopedia: Hereditary Urea Cycle Abnormality   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) ophthalmo-acromelic syndrome ?

Output: Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The features of this condition are present from birth. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma).  The most common hand and foot malformation seen in ophthalmo-acromelic syndrome is missing fingers or toes (oligodactyly). Other frequent malformations include fingers or toes that are fused together (syndactyly) or extra fingers or toes (polydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Additional skeletal abnormalities involving the long bones of the arms and legs or the spinal bones (vertebrae) can also occur. Affected individuals may have distinctive facial features, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), or intellectual disability. </s>


Input: How many people are affected by ophthalmo-acromelic syndrome ?

Output: The prevalence of ophthalmo-acromelic syndrome is not known; approximately 35 cases have been reported in the medical literature. </s>


Input: What are the genetic changes related to ophthalmo-acromelic syndrome ?

Output: Mutations in the SMOC1 gene cause ophthalmo-acromelic syndrome. The SMOC1 gene provides instructions for making a protein called secreted modular calcium-binding protein 1 (SMOC-1). This protein is found in basement membranes, which are thin, sheet-like structures that support cells in many tissues and help anchor cells to one another during embryonic development. The SMOC-1 protein attaches (binds) to many different proteins and is thought to regulate molecules called growth factors that stimulate the growth and development of tissues throughout the body. These growth factors play important roles in skeletal formation, normal shaping (patterning) of the limbs, as well as eye formation and development. The SMOC-1 protein also likely promotes the maturation (differentiation) of cells that build bones, called osteoblasts.  SMOC1 gene mutations often result in a nonfunctional SMOC-1 protein. The loss of SMOC-1 could disrupt growth factor signaling, which would impair the normal development of the skeleton, limbs, and eyes. These changes likely underlie the anophthalmia and skeletal malformations of ophthalmo-acromelic syndrome. It is unclear how SMOC1 gene mutations lead to the other features of this condition.  Some people with ophthalmo-acromelic syndrome do not have an identified mutation in the SMOC1 gene. The cause of the condition in these individuals is unknown. </s>


Input: Is ophthalmo-acromelic syndrome inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for ophthalmo-acromelic syndrome ?

Output: These resources address the diagnosis or management of ophthalmo-acromelic syndrome:  - Genetic Testing Registry: Anophthalmos with limb anomalies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) spastic paraplegia type 2 ?

Output: Spastic paraplegia type 2 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can also affect the upper limbs to a lesser degree; the structure or functioning of the brain; and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system). Spastic paraplegia type 2 can occur in either the pure or complex form.  People with the pure form of spastic paraplegia type 2 experience spasticity in the lower limbs, usually without any additional features. People with the complex form of spastic paraplegia type 2 have lower limb spasticity and can also experience problems with movement and balance (ataxia); involuntary movements of the eyes (nystagmus); mild intellectual disability; involuntary, rhythmic shaking (tremor); and degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. Symptoms usually become apparent between the ages of 1 and 5 years; those affected are typically able to walk and have a normal lifespan. </s>


Input: How many people are affected by spastic paraplegia type 2 ?

Output: The prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people worldwide. Spastic paraplegia type 2 likely accounts for only a small percentage of all spastic paraplegia cases. </s>


Input: What are the genetic changes related to spastic paraplegia type 2 ?

Output: Mutations in the PLP1 gene cause spastic paraplegia 2. The PLP1 gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of proteolipid protein 1, called DM20. Proteolipid protein 1 and DM20 are primarily located in the brain and spinal cord (central nervous system) and are the main proteins found in myelin, the fatty covering that insulates nerve fibers. A lack of proteolipid protein 1 and DM20 can cause a reduction in the formation of myelin (dysmyelination) which can impair nervous system function, resulting in the signs and symptoms of spastic paraplegia type 2. </s>


Input: Is spastic paraplegia type 2 inherited ?

Output: This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. Some females who carry a PLP1 mutation, however, may experience muscle stiffness and a decrease in intellectual function. Females with one PLP1 mutation have an increased risk of experiencing progressive deterioration of cognitive functions (dementia) later in life. </s>


Input: What are the treatments for spastic paraplegia type 2 ?

Output: These resources address the diagnosis or management of spastic paraplegia type 2:  - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview  - Gene Review: Gene Review: PLP1-Related Disorders  - Genetic Testing Registry: Spastic paraplegia 2  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) 2-hydroxyglutaric aciduria ?

Output: 2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA).  The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I.  L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.  Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood. </s>


Input: How many people are affected by 2-hydroxyglutaric aciduria ?

Output: 2-hydroxyglutaric aciduria is a rare disorder. D-2-HGA and L-2-HGA have each been reported to affect fewer than 150 individuals worldwide. Combined D,L-2-HGA appears to be even rarer, with only about a dozen reported cases. </s>


Input: What are the genetic changes related to 2-hydroxyglutaric aciduria ?

Output: The different types of 2-hydroxyglutaric aciduria result from mutations in several genes. D-2-HGA type I is caused by mutations in the D2HGDH gene; type II is caused by mutations in the IDH2 gene. L-2-HGA results from mutations in the L2HGDH gene. Combined D,L-2-HGA is caused by mutations in the SLC25A1 gene.  The D2HGDH and L2HGDH genes provide instructions for making enzymes that are found in mitochondria, which are the energy-producing centers within cells. The enzymes break down compounds called D-2-hydroxyglutarate and L-2-hydroxyglutarate, respectively, as part of a series of reactions that produce energy for cell activities. Mutations in either of these genes lead to a shortage of functional enzyme, which allows D-2-hydroxyglutarate or L-2-hydroxyglutarate to build up in cells. At high levels, these compounds can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of these compounds, which may explain why the signs and symptoms of D-2-HGA type I and L-2-HGA primarily involve the brain.  The IDH2 gene provides instructions for making an enzyme in mitochondria that normally produces a different compound. When the enzyme is altered by mutations, it takes on a new, abnormal function: production of the potentially toxic compound D-2-hydroxyglutarate. The resulting excess of this compound damages brain cells, leading to the signs and symptoms of D-2-HGA type II. It is unclear why an accumulation of D-2-hydroxyglutarate may be associated with cardiomyopathy in some people with this form of the condition.  The SLC25A1 gene provides instructions for making a protein that transports certain molecules, such as citrate, in and out of mitochondria. Mutations in the SLC25A1 gene reduce the protein's function, which prevents it from carrying out this transport. Through processes that are not fully understood, a loss of this transport allows both D-2-hydroxyglutarate and L-2-hydroxyglutarate to build up, which damages brain cells. Researchers suspect that an imbalance of other molecules, particularly citrate, also contributes to the severe signs and symptoms of combined D,L-2-HGA. </s>


Input: Is 2-hydroxyglutaric aciduria inherited ?

Output: D-2-HGA type I, L-2-HGA, and combined D,L-2-HGA all have an autosomal recessive pattern of inheritance, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  D-2-HGA type II is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. The disorder typically results from a new mutation in the IDH2 gene and occurs in people with no history of the condition in their family. </s>


Input: What are the treatments for 2-hydroxyglutaric aciduria ?

Output: These resources address the diagnosis or management of 2-hydroxyglutaric aciduria:  - Genetic Testing Registry: Combined d-2- and l-2-hydroxyglutaric aciduria  - Genetic Testing Registry: D-2-hydroxyglutaric aciduria 1  - Genetic Testing Registry: D-2-hydroxyglutaric aciduria 2  - Genetic Testing Registry: L-2-hydroxyglutaric aciduria   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Robinow syndrome ?

Output: Robinow syndrome is a rare disorder that affects the development of many parts of the body, particularly the bones. Researchers have identified two major types of Robinow syndrome. The types are distinguished by the severity of their signs and symptoms and by their pattern of inheritance, autosomal recessive or autosomal dominant.  Autosomal recessive Robinow syndrome is characterized by skeletal abnormalities including shortening of the long bones in the arms and legs, particularly the forearms; abnormally short fingers and toes (brachydactyly); wedge-shaped spinal bones (hemivertebrae) leading to an abnormal curvature of the spine (kyphoscoliosis); fused or missing ribs; and short stature. Affected individuals also have distinctive facial features, such as a broad forehead, prominent and widely spaced eyes, a short nose with an upturned tip, a wide nasal bridge, and a broad and triangle-shaped mouth. Together, these facial features are sometimes described as "fetal facies" because they resemble the facial structure of a developing fetus. Other common features of autosomal recessive Robinow syndrome include underdeveloped genitalia in both males and females, and dental problems such as crowded teeth and overgrowth of the gums. Kidney and heart defects are also possible. Delayed development occurs in 10 to 15 percent of people with this condition, although intelligence is usually normal.  Autosomal dominant Robinow syndrome has signs and symptoms that are similar to, but tend to be milder than, those of the autosomal recessive form. Abnormalities of the spine and ribs are rarely seen in the autosomal dominant form, and short stature is less pronounced. A variant form of autosomal dominant Robinow syndrome features increased bone mineral density (osteosclerosis) in addition to the signs and symptoms listed above. This variant is called the osteosclerotic form of Robinow syndrome. </s>


Input: How many people are affected by Robinow syndrome ?

Output: Both the autosomal recessive and autosomal dominant forms of Robinow syndrome are rare.  Fewer than 200 people with autosomal recessive Robinow syndrome have been described in the medical literature. This form of the condition has been identified in families from several countries, including Turkey, Oman, Pakistan, and Brazil.  Autosomal dominant Robinow syndrome has been diagnosed in fewer than 50 families; about 10 of these families have had the osteosclerotic form. </s>


Input: What are the genetic changes related to Robinow syndrome ?

Output: Autosomal recessive Robinow syndrome results from mutations in the ROR2 gene. This gene provides instructions for making a protein whose function is not well understood, although it is involved in chemical signaling pathways that are essential for normal development before birth. In particular, the ROR2 protein appears to play a critical role in the formation of the skeleton, heart, and genitals. Mutations in the ROR2 gene prevent cells from making any functional ROR2 protein, which disrupts development starting before birth and leads to the characteristic features of Robinow syndrome.  Autosomal dominant Robinow syndrome can be caused by mutations in the WNT5A or DVL1 gene, with the osteosclerotic form of the condition resulting from DVL1 gene mutations. The proteins produced from these genes appear to be part of the same chemical signaling pathways as the ROR2 protein. Mutations in either of these genes alter the production or function of their respective proteins, which impairs chemical signaling that is important for early development.  Some people with the characteristic signs and symptoms of Robinow syndrome do not have an identified mutation in the ROR2, WNT5A, or DVL1 gene. In these cases, the cause of the condition is unknown. </s>


Input: Is Robinow syndrome inherited ?

Output: As discussed above, Robinow syndrome can have either an autosomal recessive or an autosomal dominant pattern of inheritance.  Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.  Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. In some cases of Robinow syndrome, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. </s>


Input: What are the treatments for Robinow syndrome ?

Output: These resources address the diagnosis or management of Robinow syndrome:  - Gene Review: Gene Review: Autosomal Dominant Robinow Syndrome  - Gene Review: Gene Review: ROR2-Related Robinow Syndrome  - Genetic Testing Registry: Robinow syndrome  - University of Chicago: Genetic Testing for Robinow Syndrome   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Bannayan-Riley-Ruvalcaba syndrome ?

Output: Bannayan-Riley-Ruvalcaba syndrome is a genetic condition characterized by a large head size (macrocephaly), multiple noncancerous tumors and tumor-like growths called hamartomas, and dark freckles on the penis in males. The signs and symptoms of Bannayan-Riley-Ruvalcaba syndrome are present from birth or become apparent in early childhood.  At least half of affected infants have macrocephaly, and many also have a high birth weight and a large body size (macrosomia). Growth usually slows during childhood, so affected adults are of normal height and body size. About half of all children with Bannayan-Riley-Ruvalcaba syndrome have intellectual disability or delayed development, particularly the development of speech and of motor skills such as sitting, crawling, and walking. These delays may improve with age.  About half of all people with Bannayan-Riley-Ruvalcaba syndrome develop hamartomas in their intestines, known as hamartomatous polyps. Other noncancerous growths often associated with Bannayan-Riley-Ruvalcaba syndrome include fatty tumors called lipomas and angiolipomas that develop under the skin. Some affected individuals also develop hemangiomas, which are red or purplish growths that consist of tangles of abnormal blood vessels. People with Bannayan-Riley-Ruvalcaba syndrome may also have an increased risk of developing certain cancers, although researchers are still working to determine the cancer risks associated with this condition.  Other signs and symptoms that have been reported in people with Bannayan-Riley-Ruvalcaba syndrome include weak muscle tone (hypotonia) and other muscle abnormalities, thyroid problems, and seizures. Skeletal abnormalities have also been described with this condition, including an unusually large range of joint movement (hyperextensibility), abnormal side-to-side curvature of the spine (scoliosis), and a sunken chest (pectus excavatum).  The features of Bannayan-Riley-Ruvalcaba syndrome overlap with those of another disorder called Cowden syndrome. People with Cowden syndrome develop hamartomas and other noncancerous growths; they also have an increased risk of developing certain types of cancer. Both conditions can be caused by mutations in the PTEN gene. Some people with Bannayan-Riley-Ruvalcaba syndrome have had relatives diagnosed with Cowden syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Bannayan-Riley-Ruvalcaba syndrome and Cowden syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions. </s>


Input: How many people are affected by Bannayan-Riley-Ruvalcaba syndrome ?

Output: The prevalence of Bannayan-Riley-Ruvalcaba syndrome is unknown, although it appears to be rare. Several dozen cases have been reported in the medical literature. Researchers suspect that the disorder is underdiagnosed because its signs and symptoms vary and some of them are subtle. </s>


Input: What are the genetic changes related to Bannayan-Riley-Ruvalcaba syndrome ?

Output: About 60 percent of all cases of Bannayan-Riley-Ruvalcaba syndrome result from mutations in the PTEN gene. Another 10 percent of cases are caused by a large deletion of genetic material that includes part or all of this gene. The protein produced from the PTEN gene is a tumor suppressor, which means that it normally prevents cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way. If this protein is missing or defective, cell proliferation is not regulated effectively. Uncontrolled cell division can lead to the formation of hamartomas and other cancerous and noncancerous tumors. The protein produced from the PTEN gene likely has other important functions within cells; however, it is unclear how mutations in this gene can cause the other features of Bannayan-Riley-Ruvalcaba syndrome, such as macrocephaly, developmental delay, and muscle and skeletal abnormalities.  When Bannayan-Riley-Ruvalcaba syndrome is not caused by mutations or deletions of the PTEN gene, the cause of the condition is unknown. </s>


Input: Is Bannayan-Riley-Ruvalcaba syndrome inherited ?

Output: This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for Bannayan-Riley-Ruvalcaba syndrome ?

Output: These resources address the diagnosis or management of Bannayan-Riley-Ruvalcaba syndrome:  - Gene Review: Gene Review: PTEN Hamartoma Tumor Syndrome (PHTS)  - Genetic Testing Registry: Bannayan-Riley-Ruvalcaba syndrome  - University of Iowa: Bannayan-Ruvalcaba-Riley Syndrome (BRRS): A Guide for Patients and Their Families   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) aromatic l-amino acid decarboxylase deficiency ?

Output: Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disorder that affects the way signals are passed between certain cells in the nervous system.  Signs and symptoms of AADC deficiency generally appear in the first year of life. Affected infants may have severe developmental delay, weak muscle tone (hypotonia), muscle stiffness, difficulty moving, and involuntary writhing movements of the limbs (athetosis). They may be lacking in energy (lethargic), feed poorly, startle easily, and have sleep disturbances. People with AADC deficiency may also experience episodes called oculogyric crises that involve abnormal rotation of the eyeballs; extreme irritability and agitation; and pain, muscle spasms, and uncontrolled movements, especially of the head and neck.  AADC deficiency may affect the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. Resulting signs and symptoms can include droopy eyelids (ptosis), constriction of the pupils of the eyes (miosis), inappropriate or impaired sweating, nasal congestion, drooling, reduced ability to control body temperature, low blood pressure (hypotension), backflow of acidic stomach contents into the esophagus (gastroesophageal reflux), low blood sugar (hypoglycemia), fainting (syncope), and cardiac arrest.  Signs and symptoms of AADC deficiency tend to worsen late in the day or when the individual is tired, and improve after sleep. </s>


Input: How many people are affected by aromatic l-amino acid decarboxylase deficiency ?

Output: AADC deficiency is a rare disorder. Only about 100 people with this condition have been described in the medical literature worldwide; about 20 percent of these individuals are from Taiwan. </s>


Input: What are the genetic changes related to aromatic l-amino acid decarboxylase deficiency ?

Output: Mutations in the DDC gene cause AADC deficiency. The DDC gene provides instructions for making the AADC enzyme, which is important in the nervous system. This enzyme helps produce dopamine and serotonin from other molecules. Dopamine and serotonin are neurotransmitters, which are chemical messengers that transmit signals between nerve cells, both in the brain and spinal cord (central nervous system) and in other parts of the body (peripheral nervous system).  Mutations in the DDC gene result in reduced activity of the AADC enzyme. Without enough of this enzyme, nerve cells produce less dopamine and serotonin. Dopamine and serotonin are necessary for normal nervous system function, and changes in the levels of these neurotransmitters contribute to the developmental delay, intellectual disability, abnormal movements, and autonomic dysfunction seen in people with AADC deficiency. </s>


Input: Is aromatic l-amino acid decarboxylase deficiency inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for aromatic l-amino acid decarboxylase deficiency ?

Output: These resources address the diagnosis or management of aromatic l-amino acid decarboxylase deficiency:  - Genetic Testing Registry: Deficiency of aromatic-L-amino-acid decarboxylase   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) tubular aggregate myopathy ?

Output: Tubular aggregate myopathy is a disorder that primarily affects the skeletal muscles, which are muscles the body uses for movement. This disorder causes muscle pain, cramping, or weakness that begins in childhood and worsens over time. The muscles of the lower limbs are most often affected, although the upper limbs can also be involved. Affected individuals can have difficulty running, climbing stairs, or getting up from a squatting position. The weakness may also lead to an unusual walking style (gait). Some people with this condition develop joint deformities (contractures) in the arms and legs.  Skeletal muscles are normally made up of two types of fibers, called type I and type II fibers, in approximately equal quantities. Type I fibers, also called slow twitch fibers, are used for long, sustained activity, such as walking long distances. Type II fibers, also known as fast twitch fibers, are used for short bursts of strength, which are needed for activities such as running up stairs or sprinting. In people with tubular aggregate myopathy, type II fibers waste away (atrophy), so affected individuals have mostly type I fibers. In addition, proteins build up abnormally in both type I and type II fibers, forming clumps of tube-like structures called tubular aggregates. Tubular aggregates can occur in other muscle disorders, but they are the primary muscle cell abnormality in tubular aggregate myopathy. </s>


Input: How many people are affected by tubular aggregate myopathy ?

Output: Tubular aggregate myopathy is a rare disorder. Its prevalence is unknown. </s>


Input: What are the genetic changes related to tubular aggregate myopathy ?

Output: Tubular aggregate myopathy can be caused by mutations in the STIM1 gene. The protein produced from this gene is involved in controlling the entry of positively charged calcium atoms (calcium ions) into cells. The STIM1 protein recognizes when calcium ion levels are low and stimulates the flow of ions into the cell through special channels in the cell membrane called calcium-release activated calcium (CRAC) channels. In muscle cells, the activation of CRAC channels by STIM1 is thought to help replenish calcium stores in a structure called the sarcoplasmic reticulum. STIM1 may also be involved in the release of calcium ions from the sarcoplasmic reticulum. This release of ions stimulates muscle tensing (contraction).  The STIM1 gene mutations involved in tubular aggregate myopathy lead to production of a STIM1 protein that is constantly turned on (constitutively active), which means it continually stimulates calcium ion entry through CRAC channels regardless of ion levels. It is unknown how constitutively active STIM1 leads to the muscle weakness characteristic of tubular aggregate myopathy. Evidence suggests that the tubular aggregates are composed of proteins that are normally part of the sarcoplasmic reticulum. Although the mechanism is unknown, some researchers speculate that the aggregates are the result of uncontrolled calcium levels in muscle cells, possibly due to abnormal STIM1 activity.  Mutations in other genes, some of which have not been identified, are also thought to cause some cases of tubular aggregate myopathy. </s>


Input: Is tubular aggregate myopathy inherited ?

Output: Most cases of tubular aggregate myopathy, including those caused by STIM1 gene mutations, are inherited in an autosomal dominant pattern. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, the mutation is passed through generations in a family. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.  Rarely, tubular aggregate myopathy is inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Researchers are still working to determine which gene or genes are associated with autosomal recessive tubular aggregate myopathy. </s>


Input: What are the treatments for tubular aggregate myopathy ?

Output: These resources address the diagnosis or management of tubular aggregate myopathy:  - Genetic Testing Registry: Myopathy with tubular aggregates   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) arginine:glycine amidinotransferase deficiency ?

Output: Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. People with this disorder have mild to moderate intellectual disability and delayed speech development. Some affected individuals develop autistic behaviors that affect communication and social interaction. They may experience seizures, especially when they have a fever.  Children with arginine:glycine amidinotransferase deficiency may not gain weight and grow at the expected rate (failure to thrive), and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily. </s>


Input: How many people are affected by arginine:glycine amidinotransferase deficiency ?

Output: The prevalence of arginine:glycine amidinotransferase deficiency is unknown. The disorder has been identified in only a few families. </s>


Input: What are the genetic changes related to arginine:glycine amidinotransferase deficiency ?

Output: Mutations in the GATM gene cause arginine:glycine amidinotransferase deficiency. The GATM gene provides instructions for making the enzyme arginine:glycine amidinotransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, arginine:glycine amidinotransferase controls the first step of the process. In this step, a compound called guanidinoacetic acid is produced by transferring a cluster of nitrogen and hydrogen atoms called a guanidino group from arginine to glycine. Guanidinoacetic acid is converted to creatine in the second step of the process. Creatine is needed for the body to store and use energy properly.  GATM gene mutations impair the ability of the arginine:glycine amidinotransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of arginine:glycine amidinotransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain. </s>


Input: Is arginine:glycine amidinotransferase deficiency inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for arginine:glycine amidinotransferase deficiency ?

Output: These resources address the diagnosis or management of arginine:glycine amidinotransferase deficiency:  - Gene Review: Gene Review: Creatine Deficiency Syndromes  - Genetic Testing Registry: Arginine:glycine amidinotransferase deficiency   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) Tangier disease ?

Output: Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease.  Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood (mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the clear covering of the eye (corneal clouding), and type 2 diabetes. </s>


Input: How many people are affected by Tangier disease ?

Output: Tangier disease is a rare disorder with approximately 100 cases identified worldwide. More cases are likely undiagnosed. This condition is named after an island off the coast of Virginia where the first affected individuals were identified. </s>


Input: What are the genetic changes related to Tangier disease ?

Output: Mutations in the ABCA1 gene cause Tangier disease. This gene provides instructions for making a protein that releases cholesterol and phospholipids from cells. These substances are used to make HDL, which transports them to the liver.  Mutations in the ABCA1 gene prevent the release of cholesterol and phospholipids from cells. As a result, these substances accumulate within cells, causing certain body tissues to enlarge and the tonsils to acquire a yellowish-orange color. A buildup of cholesterol can be toxic to cells, leading to impaired cell function or cell death. In addition, the inability to transport cholesterol and phospholipids out of cells results in very low HDL levels, which increases the risk of cardiovascular disease. These combined factors cause the signs and symptoms of Tangier disease. </s>


Input: Is Tangier disease inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for Tangier disease ?

Output: These resources address the diagnosis or management of Tangier disease:  - Genetic Testing Registry: Tangier disease   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) prekallikrein deficiency ?

Output: Prekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons.  A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency. </s>


Input: How many people are affected by prekallikrein deficiency ?

Output: The prevalence of prekallikrein deficiency is unknown. Approximately 80 affected individuals in about 30 families have been described in the medical literature. Because prekallikrein deficiency usually does not cause any symptoms, researchers suspect that most people with the condition are never diagnosed. </s>


Input: What are the genetic changes related to prekallikrein deficiency ?

Output: Prekallikrein deficiency is caused by mutations in the KLKB1 gene, which provides instructions for making a protein called prekallikrein. This protein, when converted to an active form called plasma kallikrein in the blood, is involved in the early stages of blood clotting. Plasma kallikrein plays a role in a process called the intrinsic coagulation pathway (also called the contact activation pathway). This pathway turns on (activates) proteins that are needed later in the clotting process. Blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss.  The KLKB1 gene mutations that cause prekallikrein deficiency reduce or eliminate functional plasma kallikrein, which likely impairs the intrinsic coagulation pathway. Researchers suggest that this lack (deficiency) of functional plasma kallikrein protein does not generally cause any symptoms because another process called the extrinsic coagulation pathway (also known as the tissue factor pathway) can compensate for the impaired intrinsic coagulation pathway. </s>


Input: Is prekallikrein deficiency inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>


Input: What are the treatments for prekallikrein deficiency ?

Output: These resources address the diagnosis or management of prekallikrein deficiency:  - Genetic Testing Registry: Prekallikrein deficiency  - Massachusetts General Hospital Laboratory Handbook: Prekallikrein   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care </s>


Input: What is (are) congenital generalized lipodystrophy ?

Output: Congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) is a rare condition characterized by an almost total lack of fatty (adipose) tissue in the body and a very muscular appearance. Adipose tissue is found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat for energy and also provides cushioning. Congenital generalized lipodystrophy is part of a group of related disorders known as lipodystrophies, which are all characterized by a loss of adipose tissue. A shortage of adipose tissue leads to the storage of fat elsewhere in the body, such as in the liver and muscles, which causes serious health problems.  The signs and symptoms of congenital generalized lipodystrophy are usually apparent from birth or early childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are unable to recognize insulin, a hormone that normally helps to regulate blood sugar levels. Insulin resistance may develop into a more serious disease called diabetes mellitus. Most affected individuals also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to the development of small yellow deposits of fat under the skin called eruptive xanthomas and inflammation of the pancreas (pancreatitis). Additionally, congenital generalized lipodystrophy causes an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and liver failure. Some affected individuals develop a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and an abnormal heart rhythm (arrhythmia) that can cause sudden death.  People with congenital generalized lipodystrophy have a distinctive physical appearance. They appear very muscular because they have an almost complete absence of adipose tissue and an overgrowth of muscle tissue. A lack of adipose tissue under the skin also makes the veins appear prominent. Affected individuals tend to have a large chin, prominent bones above the eyes (orbital ridges), large hands and feet, and a prominent belly button (umbilicus). Affected females may have an enlarged clitoris (clitoromegaly), an increased amount of body hair (hirsutism), irregular menstrual periods, and multiple cysts on the ovaries, which may be related to hormonal changes. Many people with this disorder develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.  Researchers have described four types of congenital generalized lipodystrophy, which are distinguished by their genetic cause. The types also have some differences in their typical signs and symptoms. For example, in addition to the features described above, some people with congenital generalized lipodystrophy type 1 develop cysts in the long bones of the arms and legs after puberty. Type 2 can be associated with intellectual disability, which is usually mild to moderate. Type 3 appears to cause poor growth and short stature, along with other health problems. Type 4 is associated with muscle weakness, delayed development, joint abnormalities, a narrowing of the lower part of the stomach (pyloric stenosis), and severe arrhythmia that can lead to sudden death. </s>


Input: How many people are affected by congenital generalized lipodystrophy ?

Output: Congenital generalized lipodystrophy has an estimated prevalence of 1 in 10 million people worldwide. Between 300 and 500 people with the condition have been described in the medical literature. Although this condition has been reported in populations around the world, it appears to be more common in certain regions of Lebanon and Brazil. </s>


Input: What are the genetic changes related to congenital generalized lipodystrophy ?

Output: Mutations in the AGPAT2, BSCL2, CAV1, and PTRF genes cause congenital generalized lipodystrophy types 1 through 4, respectively. The proteins produced from these genes play important roles in the development and function of adipocytes, which are the fat-storing cells in adipose tissue. Mutations in any of these genes reduce or eliminate the function of their respective proteins, which impairs the development, structure, or function of adipocytes and makes the body unable to store and use fats properly. These abnormalities of adipose tissue disrupt hormones and affect many of the body's organs, resulting in the varied signs and symptoms of congenital generalized lipodystrophy.  Some of the genes associated with congenital generalized lipodystrophy also play roles in other cells and tissues. For example, the protein produced from the BSCL2 gene is also present in the brain, although its function is unknown. A loss of this protein in the brain may help explain why congenital generalized lipodystrophy type 2 is sometimes associated with intellectual disability.  In some people with congenital generalized lipodystrophy, no mutations have been found in any of the genes listed above. Researchers are looking for additional genetic changes associated with this disorder. </s>


Input: Is congenital generalized lipodystrophy inherited ?

Output: This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. </s>