Input: What is (are) renal tubular dysgenesis ?

Output: Renal tubular dysgenesis is a severe kidney disorder characterized by abnormal development of the kidneys before birth. In particular, kidney structures called proximal tubules are absent or underdeveloped. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete everything else into the urine. Without functional proximal tubules, the kidneys cannot produce urine (a condition called anuria).  Fetal urine is the major component of the fluid that surrounds the fetus (amniotic fluid), and anuria leads to decreased amniotic fluid levels (oligohydramnios). Amniotic fluid helps cushion and protect the fetus and plays a role in the development of many organs, including the lungs. Oligohydramnios causes a set of abnormalities called the Potter sequence, which includes distinctive facial features such as a flattened nose and large, low-set ears; excess skin; inward- and upward-turning feet (clubfeet); and underdeveloped lungs.  Renal tubular dysgenesis also causes severe low blood pressure (hypotension). In addition, bone development in the skull is abnormal in some affected individuals, causing a large space between the bones of the skull (fontanels).  As a result of the serious health problems caused by renal tubular dysgenesis, affected individuals usually die before birth, are stillborn, or die soon after birth from respiratory failure. Rarely, with treatment, affected individuals survive into childhood. Their blood pressure usually normalizes, but they quickly develop chronic kidney disease, which is characterized by reduced kidney function that worsens over time. </s>


Input: How many people are affected by renal tubular dysgenesis ?

Output: Renal tubular dysgenesis is a rare disorder, but its prevalence is unknown. </s>


Input: What are the genetic changes related to renal tubular dysgenesis ?

Output: Mutations in the ACE, AGT, AGTR1, or REN gene can cause renal tubular dysgenesis. These genes are involved in the renin-angiotensin system, which regulates blood pressure and the balance of fluids and salts in the body and plays a role in kidney development before birth.  The renin-angiotensin system consists of several proteins that are involved in a series of steps to produce a protein called angiotensin II. In the first step, the renin protein (produced from the REN gene) converts a protein called angiotensinogen (produced from the AGT gene) to angiotensin I. In the next step, angiotensin-converting enzyme (produced from the ACE gene) converts angiotensin I to angiotensin II. Angiotensin II attaches (binds) to the angiotensin II receptor type 1 (AT1 receptor; produced from the AGTR1 gene), stimulating chemical signaling.  By binding to the AT1 receptor, angiotensin II causes blood vessels to narrow (constrict), which results in increased blood pressure. This protein also stimulates production of the hormone aldosterone, which triggers the absorption of salt and water by the kidneys. The increased amount of fluid in the body also increases blood pressure. Proper blood pressure, which delivers oxygen to the developing tissues during fetal growth, is required for normal development of the kidneys (particularly of the proximal tubules) and other tissues.  Mutations in the ACE, AGT, AGTR1, or REN gene impair the production or function of angiotensin II, leading to a nonfunctional renin-angiotensin system. Without this system, the kidneys cannot control blood pressure. Because of low blood pressure, the flow of blood is reduced (hypoperfusion), and the fetal tissues do not get enough oxygen during development. As a result, kidney development is impaired, leading to the features of renal tubular dysgenesis. Hypoperfusion also causes the skull abnormalities found in individuals with this condition.  Medications that block the activity of the angiotensin-converting enzyme or the AT1 receptor are used to treat high blood pressure. Because these drugs impair the renin-angiotensin system, they can cause an acquired (non-inherited) form of renal tubular dysgenesis in fetuses of pregnant women who take them. Acquired renal tubular dysgenesis can also result from other conditions that cause renal hypoperfusion during fetal development. These include heart problems, congenital hemochromatosis, and a complication that can occur in twin pregnancies called twin-to-twin transfusion syndrome. </s>


Input: Is renal tubular dysgenesis inherited ?

Output: Renal tubular dysgenesis is inherited in an autosomal recessive pattern, which means both copies of the affected 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 renal tubular dysgenesis ?

Output: These resources address the diagnosis or management of renal tubular dysgenesis:  - Genetic Testing Registry: Renal dysplasia   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) Crohn disease ?

Output: Crohn disease is a complex, chronic disorder that primarily affects the digestive system. This condition typically involves abnormal inflammation of the intestinal walls, particularly in the lower part of the small intestine (the ileum) and portions of the large intestine (the colon). Inflammation can occur in any part of the digestive system, however. The inflamed tissues become thick and swollen, and the inner surface of the intestine may develop open sores (ulcers).  Crohn disease most commonly appears in a person's late teens or twenties, although the disease can appear at any age. Signs and symptoms tend to flare up multiple times throughout life. The most common features of this condition are persistent diarrhea, abdominal pain and cramping, loss of appetite, weight loss, and fever. Some people with Crohn disease have chronic bleeding from inflamed tissues in the intestine; over time, this bleeding can lead to a low number of red blood cells (anemia). In some cases, Crohn disease can also cause medical problems affecting the joints, eyes, or skin.  Intestinal blockage is a common complication of Crohn disease. Blockages are caused by swelling or a buildup of scar tissue in the intestinal walls. Some affected individuals also develop fistulae, which are abnormal connections between the intestine and other tissues. Fistulae occur when ulcers break through the intestinal wall to form passages between loops of the intestine or between the intestine and nearby structures (such as the bladder, vagina, or skin).  Crohn disease is one common form of inflammatory bowel disease (IBD). Another type of IBD, ulcerative colitis, also causes chronic inflammation of the intestinal lining. Unlike Crohn disease, which can affect any part of the digestive system, ulcerative colitis typically causes inflammation only in the colon. In addition, the two disorders involve different patterns of inflammation. </s>


Input: How many people are affected by Crohn disease ?

Output: Crohn disease is most common in western Europe and North America, where it affects 100 to 150 in 100,000 people. About one million Americans are currently affected by this disorder. Crohn disease occurs more often in whites and people of eastern and central European (Ashkenazi) Jewish descent than among people of other ethnic backgrounds. </s>


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

Output: Crohn disease is related to chromosomes 5 and 10.  Variations of the ATG16L1, IRGM, and NOD2 genes increase the risk of developing Crohn disease.  The IL23R gene is associated with Crohn disease.  A variety of genetic and environmental factors likely play a role in causing Crohn disease. Although researchers are studying risk factors that may contribute to this complex disorder, many of these factors remain unknown. Cigarette smoking is thought to increase the risk of developing this disease, and it may also play a role in periodic flare-ups of signs and symptoms.  Studies suggest that Crohn disease may result from a combination of certain genetic variations, changes in the immune system, and the presence of bacteria in the digestive tract. Recent studies have identified variations in specific genes, including ATG16L1, IL23R, IRGM, and NOD2, that influence the risk of developing Crohn disease. These genes provide instructions for making proteins that are involved in immune system function. Variations in any of these genes may disrupt the ability of cells in the intestine to respond normally to bacteria. An abnormal immune response to bacteria in the intestinal walls may lead to chronic inflammation and the digestive problems characteristic of Crohn disease.  Researchers have also discovered genetic variations in certain regions of chromosome 5 and chromosome 10 that appear to contribute to Crohn disease risk. One area of chromosome 5, known as the IBD5 locus, contains several genetic changes that may increase the risk of developing this condition. Other regions of chromosome 5 and chromosome 10 identified in studies of Crohn disease risk are known as "gene deserts" because they include no known genes. Instead, these regions may contain stretches of DNA that regulate nearby genes. Additional research is needed to determine how genetic variations in these chromosomal regions are related to a person's chance of developing Crohn disease. </s>


Input: Is Crohn disease inherited ?

Output: The inheritance pattern of Crohn disease is unclear because many genetic and environmental factors are likely to be involved. This condition tends to cluster in families, however, and having an affected family member is a significant risk factor for the disease. </s>


Input: What are the treatments for Crohn disease ?

Output: These resources address the diagnosis or management of Crohn disease:  - Genetic Testing Registry: Inflammatory bowel disease 1  - MedlinePlus Encyclopedia: Crohn's 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) antiphospholipid syndrome ?

Output: Antiphospholipid syndrome is a disorder characterized by an increased tendency to form abnormal blood clots (thromboses) that can block blood vessels. This clotting tendency is known as thrombophilia. In antiphospholipid syndrome, the thromboses can develop in nearly any blood vessel in the body, but most frequently occur in the vessels of the lower limbs. If a blood clot forms in the vessels in the brain, blood flow is impaired and can lead to stroke. Antiphospholipid syndrome is an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs.  Women with antiphospholipid syndrome are at increased risk of complications during pregnancy. These complications include pregnancy-induced high blood pressure (preeclampsia), an underdeveloped placenta (placental insufficiency), early delivery, or pregnancy loss (miscarriage). In addition, women with antiphospholipid syndrome are at greater risk of having a thrombosis during pregnancy than at other times during their lives. At birth, infants of mothers with antiphospholipid syndrome may be small and underweight.  A thrombosis or pregnancy complication is typically the first sign of antiphospholipid syndrome. This condition usually appears in early to mid-adulthood but can begin at any age.  Other signs and symptoms of antiphospholipid syndrome that affect blood cells and vessels include a reduced amount of blood clotting cells called platelets (thrombocytopenia), a shortage of red blood cells (anemia) due to their premature breakdown (hemolysis), and a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin. In addition, affected individuals may have open sores (ulcers) on the skin, migraine headaches, heart disease, or intellectual disability. Many people with antiphospholipid syndrome also have other autoimmune disorders such as systemic lupus erythematosus.  Rarely, people with antiphospholipid syndrome develop thromboses in multiple blood vessels throughout their body. These thromboses block blood flow in affected organs, which impairs their function and ultimately causes organ failure. These individuals are said to have catastrophic antiphospholipid syndrome (CAPS). CAPS typically affects the kidneys, lungs, brain, heart, and liver, and is fatal in over half of affected individuals. Less than 1 percent of individuals with antiphospholipid syndrome develop CAPS. </s>


Input: How many people are affected by antiphospholipid syndrome ?

Output: The exact prevalence of antiphospholipid syndrome is unknown. This condition is thought to be fairly common, and may be responsible for up to one percent of all thromboses. It is estimated that 20 percent of individuals younger than age 50 who have a stroke have antiphospholipid syndrome. Ten to 15 percent of people with systemic lupus erythematosus have antiphospholipid syndrome. Similarly, 10 to 15 percent of women with recurrent miscarriages likely have this condition. Approximately 70 percent of individuals diagnosed with antiphospholipid syndrome are female. </s>


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

Output: The genetic cause of antiphospholipid syndrome is unknown. This condition is associated with the presence of three abnormal immune proteins (antibodies) in the blood: lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibodies in antiphospholipid syndrome attack normal human proteins. When these antibodies attach (bind) to proteins, the proteins change shape and bind to other molecules and receptors on the surface of cells. Binding to cells, particularly immune cells, turns on (activates) the blood clotting pathway and other immune responses.  The production of lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I may coincide with exposure to foreign invaders, such as viruses and bacteria, that are similar to normal human proteins. Exposure to these foreign invaders may cause the body to produce antibodies to fight the infection, but because the invaders are so similar to the body's own proteins, the antibodies also attack the human proteins. Similar triggers may occur during pregnancy when a woman's physiology, particularly her immune system, adapts to accommodate the developing fetus. These changes during pregnancy may explain the high rate of affected females.  Certain genetic variations (polymorphisms) in a few genes have been found in people with antiphospholipid syndrome and may predispose individuals to produce the specific antibodies known to contribute to the formation of thromboses. However, the contribution of these genetic changes to the development of the condition is unclear.  People who test positive for all three antibodies but have not had a thrombosis or recurrent miscarriages are said to be antiphospholipid carriers. These individuals are at greater risk of developing a thrombosis than is the general population. </s>


Input: Is antiphospholipid syndrome inherited ?

Output: Most cases of antiphospholipid syndrome are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance. Multiple genetic and environmental factors likely play a part in determining the risk of developing antiphospholipid syndrome. </s>


Input: What are the treatments for antiphospholipid syndrome ?

Output: These resources address the diagnosis or management of antiphospholipid syndrome:  - Genetic Testing Registry: Antiphospholipid syndrome  - Hughes Syndrome Foundation: Diagnosis: How To Get Tested  - Hughes Syndrome Foundation: Treatment and Medication: Current Advice and Information  - National Heart Lung and Blood Institute: How Is Antiphospholipid Antibody Syndrome Treated?   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) adiposis dolorosa ?

Output: Adiposis dolorosa is a condition characterized by painful folds of fatty (adipose) tissue or the growth of multiple noncancerous (benign) fatty tumors called lipomas. This condition occurs most often in women who are overweight or obese, and signs and symptoms typically appear between ages 35 and 50.  In people with adiposis dolorosa, abnormal fatty tissue or lipomas can occur anywhere on the body but are most often found on the torso, buttocks, and upper parts of the arms and legs. Lipomas usually feel like firm bumps (nodules) under the skin. The growths cause burning or aching that can be severe. In some people, the pain comes and goes, while in others it is continuous. Movement or pressure on adipose tissue or lipomas can make the pain worse.  Other signs and symptoms that have been reported to occur with adiposis dolorosa include general weakness and tiredness (fatigue), depression, irritability, confusion, recurrent seizures (epilepsy), and a progressive decline in intellectual function (dementia). These problems do not occur in everyone with adiposis dolorosa, and it is unclear whether they are directly related to the condition. </s>


Input: How many people are affected by adiposis dolorosa ?

Output: Adiposis dolorosa is a rare condition whose prevalence is unknown. For reasons that are unclear, it occurs up to 30 times more often in women than in men. </s>


Input: What are the genetic changes related to adiposis dolorosa ?

Output: The cause of adiposis dolorosa is unknown. The condition is thought to have a genetic component because a few families with multiple affected family members have been reported. However, no associated genes have been identified.  Several other possible causes of adiposis dolorosa have been suggested, although none have been confirmed. They include the use of medications called corticosteroids, dysfunction of the endocrine system (which produces hormones), or changes in the deposition and breakdown of fat (adipose tissue metabolism). Researchers have also suggested that adiposis dolorosa could be an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's own tissues and organs. However, there is no firm evidence that the condition is related to abnormal inflammation or other immune system malfunction.  It is unknown why adiposis dolorosa usually occurs in people who are overweight or obese, or why the signs and symptoms do not appear until mid-adulthood. </s>


Input: Is adiposis dolorosa inherited ?

Output: Most cases of adiposis dolorosa are sporadic, which means they occur in people with no history of the disorder in their family.  A small number of familial cases of adiposis dolorosa have been reported. When the condition runs in families, it appears to have an autosomal dominant pattern of inheritance because affected individuals inherit the condition from one affected parent. This pattern of inheritance suggests that one copy of an altered gene in each cell is sufficient to cause the disorder. </s>


Input: What are the treatments for adiposis dolorosa ?

Output: These resources address the diagnosis or management of adiposis dolorosa:  - Genetic Testing Registry: Lipomatosis dolorosa  - Merck Manual Consumer Version: Lipomas   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) CATSPER1-related nonsyndromic male infertility ?

Output: CATSPER1-related nonsyndromic male infertility is a condition that affects the function of sperm, leading to an inability to father children. Males with this condition produce sperm that have decreased movement (motility). Affected men may also produce a smaller than usual number of sperm cells or sperm cells that are abnormally shaped. Men with CATSPER1-related nonsyndromic male infertility do not have any other symptoms related to this condition. </s>


Input: How many people are affected by CATSPER1-related nonsyndromic male infertility ?

Output: The prevalence of CATSPER1-related nonsyndromic male infertility is unknown. </s>


Input: What are the genetic changes related to CATSPER1-related nonsyndromic male infertility ?

Output: Mutations in the CATSPER1 gene cause CATSPER1-related nonsyndromic male infertility. The CATSPER1 gene provides instructions for producing a protein that is found in the tail of sperm cells. The CATSPER1 protein is involved in the movement of the sperm tail, which propels the sperm forward and is required for sperm cells to push through the outside membrane of the egg cell during fertilization.  CATSPER1 gene mutations result in the production of a CATSPER1 protein that may be altered, nonfunctional, or quickly broken down (degraded) by the cell. Sperm cells missing a functional CATSPER1 protein have decreased motion in their tails and move more slowly than normal. Sperm cells lacking functional CATSPER1 protein cannot push through the outside membrane of the egg cell. As a result, sperm cells cannot reach the inside of the egg cell to achieve fertilization. </s>


Input: Is CATSPER1-related nonsyndromic male infertility 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 symptoms of the condition.  Males with two CATSPER1 gene mutations in each cell have CATSPER1-related nonsyndromic male infertility. Females with two CATSPER1 gene mutations in each cell have no symptoms because the mutations only affect sperm function, and women do not produce sperm. </s>


Input: What are the treatments for CATSPER1-related nonsyndromic male infertility ?

Output: These resources address the diagnosis or management of CATSPER1-related nonsyndromic male infertility:  - Cleveland Clinic: Male Infertility  - Gene Review: Gene Review: CATSPER-Related Male Infertility  - Genetic Testing Registry: CATSPER-Related Male Infertility  - MedlinePlus Health Topic: Assisted Reproductive Technology  - RESOLVE: The National Infertility Association: Semen Analysis   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) Aicardi-Goutieres syndrome ?

Output: Aicardi-Goutieres syndrome is a disorder that mainly affects the brain, the immune system, and the skin.  Most newborns with Aicardi-Goutieres syndrome do not show any signs or symptoms of the disorder at birth. However, about 20 percent are born with a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, a decrease in blood platelets (thrombocytopenia), and abnormal neurological responses. While this combination of signs and symptoms is typically associated with the immune system's response to congenital viral infection, no actual infection is found in these infants. For this reason, Aicardi-Goutieres syndrome is sometimes referred to as a "mimic of congenital infection."  Within the first year of life most individuals with Aicardi-Goutieres syndrome experience an episode of severe brain dysfunction (encephalopathy), typically lasting for several months. During this phase of the disorder, affected babies are usually extremely irritable and do not feed well. They may develop intermittent fevers in the absence of infection (sterile pyrexias) and may have seizures. They stop developing new skills and begin losing skills they had already acquired (developmental regression). Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). In this phase of the disorder, white blood cells and molecules associated with inflammation can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These abnormal findings are consistent with inflammation and tissue damage in the central nervous system.  The encephalopathic phase of Aicardi-Goutieres syndrome leaves behind permanent neurological damage that is usually severe. Medical imaging reveals deterioration of white matter in the brain (leukodystrophy). White matter consists of nerve fibers covered by myelin, which is a substance that insulates and protects nerves. Affected individuals also have abnormal deposits of calcium (calcification) in the brain.  Most people with Aicardi-Goutieres syndrome have profound intellectual disability. They also have significant neuromuscular problems including muscle stiffness (spasticity); involuntary tensing of various muscles (dystonia), especially those in the arms; and weak muscle tone (hypotonia) in the trunk.  About 40 percent of people with Aicardi-Goutieres syndrome have painful, itchy skin lesions, usually on the fingers, toes, and ears. These puffy, red lesions, which are called chilblains, are caused by inflammation of small blood vessels. They may be brought on or made worse by exposure to cold. Vision problems, joint stiffness, and mouth ulcers may also occur in this disorder.  As a result of the severe neurological problems usually associated with Aicardi-Goutieres syndrome, most people with this disorder do not survive past childhood. However, some affected individuals who have later onset and milder neurological problems may live into adulthood. </s>


Input: How many people are affected by Aicardi-Goutieres syndrome ?

Output: Aicardi-Goutieres syndrome is a rare disorder. Its exact prevalence is unknown. </s>


Input: What are the genetic changes related to Aicardi-Goutieres syndrome ?

Output: Mutations in the TREX1, RNASEH2A, RNASEH2B, RNASEH2C, and SAMHD1 genes have been identified in people with Aicardi-Goutieres syndrome.  The TREX1, RNASEH2A, RNASEH2B, and RNASEH2C genes provide instructions for making nucleases, which are enzymes that help break up molecules of DNA and its chemical cousin RNA. Mutations in any of these genes are believed to result in an absent or dysfunctional nuclease enzyme. Researchers suggest that absent or impaired enzyme function may result in the accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules or fragments may be generated during the first stage of protein production (transcription), copying (replication) of cells' genetic material in preparation for cell division, DNA repair, cell death, and other processes. The unneeded DNA and RNA may be mistaken by cells for that of viral invaders, triggering immune system reactions that result in encephalopathy, skin lesions, and other signs and symptoms of Aicardi-Goutieres syndrome.  The SAMHD1 gene provides instructions for making a protein whose function is not well understood; however, it is believed to be involved in the immune system and the inflammatory process. Mutations in this gene likely result in a protein that does not function properly, resulting in immune system abnormalities, inflammatory damage to the brain and skin, and other characteristics of Aicardi-Goutieres syndrome. </s>


Input: Is Aicardi-Goutieres syndrome inherited ?

Output: Aicardi-Goutieres syndrome can have different inheritance patterns. In most cases it 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.  Rarely, 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. These 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 Aicardi-Goutieres syndrome ?

Output: These resources address the diagnosis or management of Aicardi-Goutieres syndrome:  - Gene Review: Gene Review: Aicardi-Goutieres Syndrome  - Genetic Testing Registry: Aicardi Goutieres syndrome  - Genetic Testing Registry: Aicardi Goutieres syndrome 1  - Genetic Testing Registry: Aicardi Goutieres syndrome 2  - Genetic Testing Registry: Aicardi Goutieres syndrome 3  - Genetic Testing Registry: Aicardi Goutieres syndrome 4  - Genetic Testing Registry: Aicardi Goutieres syndrome 5   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) microcephaly-capillary malformation syndrome ?

Output: Microcephaly-capillary malformation syndrome is an inherited disorder characterized by an abnormally small head size (microcephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).  In people with microcephaly-capillary malformation syndrome, microcephaly begins before birth and is associated with an unusually small brain and multiple brain abnormalities. Affected individuals develop seizures that can occur many times per day and are difficult to treat (intractable epilepsy). The problems with brain development and epilepsy lead to profound developmental delay and intellectual impairment. Most affected individuals do not develop skills beyond those of a 1- or 2-month-old infant. For example, most children with this condition are never able to control their head movements or sit unassisted.  Capillary malformations are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like pink or red spots on the skin. People with microcephaly-capillary malformation syndrome are born with anywhere from a few to hundreds of these spots, which can occur anywhere on the body. The spots are usually round or oval-shaped and range in size from the head of a pin to a large coin.  Other signs and symptoms of microcephaly-capillary malformation syndrome include abnormal movements, feeding difficulties, slow growth, and short stature. Most affected individuals have abnormalities of the fingers and toes, including digits with tapered ends and abnormally small or missing fingernails and toenails. Some affected children also have distinctive facial features and an unusual pattern of hair growth on the scalp. </s>


Input: How many people are affected by microcephaly-capillary malformation syndrome ?

Output: Microcephaly-capillary malformation syndrome is rare. About a dozen people have been diagnosed with the disorder. </s>


Input: What are the genetic changes related to microcephaly-capillary malformation syndrome ?

Output: Microcephaly-capillary malformation syndrome results from mutations in the STAMBP gene. This gene provides instructions for making a protein called STAM binding protein. This protein plays a role in sorting damaged or unneeded proteins so they can be transported from the cell surface to specialized cell compartments that break down (degrade) or recycle them. This process helps to maintain the proper balance of protein production and breakdown (protein homeostasis) that cells need to function and survive. Studies suggest that STAM binding protein is also involved in multiple chemical signaling pathways within cells, including pathways needed for overall growth and the formation of new blood vessels (angiogenesis).  Mutations in the STAMBP gene reduce or eliminate the production of STAM binding protein. This shortage allows damaged or unneeded proteins to build up inside cells instead of being degraded or recycled, which may damage cells and cause them to self-destruct (undergo apoptosis). Researchers suspect that abnormal apoptosis of brain cells starting before birth may cause microcephaly and the underlying brain abnormalities found in people with microcephaly-capillary malformation syndrome. A lack of STAM binding protein also alters multiple signaling pathways that are necessary for normal development, which may underlie the capillary malformations and other signs and symptoms of the condition. </s>


Input: Is microcephaly-capillary malformation syndrome inherited ?

Output: This condition has an autosomal recessive pattern of inheritance, which means both copies of the STAMBP gene in each cell have mutations. An affected individual usually inherits one altered copy of the gene from each parent. Parents of an individual with an autosomal recessive condition typically do not show signs and symptoms of the condition.  At least one individual with microcephaly-capillary malformation syndrome inherited two mutated copies of the STAMBP gene through a mechanism called uniparental isodisomy. In this case, an error occurred during the formation of egg or sperm cells, and the child received two copies of the mutated gene from one parent instead of one copy from each parent. </s>


Input: What are the treatments for microcephaly-capillary malformation syndrome ?

Output: These resources address the diagnosis or management of microcephaly-capillary malformation syndrome:  - Gene Review: Gene Review: Microcephaly-Capillary Malformation Syndrome  - Genetic Testing Registry: Microcephaly-capillary malformation 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) atopic dermatitis ?

Output: Atopic dermatitis (also known as atopic eczema) is a disorder characterized by inflammation of the skin (dermatitis). The condition usually begins in early infancy, and it often disappears before adolescence. However, in some affected individuals the condition continues into adulthood or does not begin until adulthood. Hallmarks of atopic dermatitis include dry, itchy skin and red rashes that can come and go. The rashes can occur on any part of the body, although the pattern tends to be different at different ages. In affected infants, the rashes commonly occur on the face, scalp, hands, and feet. In children, the rashes are usually found in the bend of the elbows and knees and on the front of the neck. In adolescents and adults, the rashes typically occur on the wrists, ankles, and eyelids in addition to the bend of the elbows and knees. Scratching the itchy skin can lead to oozing and crusting of the rashes and thickening and hardening (lichenification) of the skin. The itchiness can be so severe as to disturb sleep and impair a person's quality of life.  The word "atopic" indicates an association with allergies. While atopic dermatitis is not always due to an allergic reaction, it is commonly associated with other allergic disorders: up to 60 percent of people with atopic dermatitis develop asthma or hay fever (allergic rhinitis) later in life, and up to 30 percent have food allergies. Atopic dermatitis is often the beginning of a series of allergic disorders, referred to as the atopic march. Development of these disorders typically follows a pattern, beginning with atopic dermatitis, followed by food allergies, then hay fever, and finally asthma. However, not all individuals with atopic dermatitis will progress through the atopic march, and not all individuals with one allergic disease will develop others.  Individuals with atopic dermatitis have an increased risk of developing other conditions related to inflammation, such as inflammatory bowel disease and rheumatoid arthritis. They are also more likely than individuals of the general public to have a behavioral or psychiatric disorder, such as attention deficit hyperactivity disorder (ADHD) or depression. </s>


Input: How many people are affected by atopic dermatitis ?

Output: Atopic dermatitis is a common disorder that affects 10 to 20 percent of children and 5 to 10 percent of adults. </s>


Input: What are the genetic changes related to atopic dermatitis ?

Output: The genetics of atopic dermatitis are not completely understood. Studies suggest that several genes can be involved in development of the condition. The strongest association is with the FLG gene, which is mutated in 20 to 30 percent of people with atopic dermatitis compared with 8 to 10 percent of the general population without atopic dermatitis.  The FLG gene provides instructions for making a protein called profilaggrin, which is cut (cleaved) to produce multiple copies of the filaggrin protein. Filaggrin is involved in creating the structure of the outermost layer of skin, creating a strong barrier to keep in water and keep out foreign substances, including toxins, bacteria, and substances that can cause allergic reactions (allergens), such as pollen and dust. Further processing of the filaggrin protein produces other molecules that are part of the skin's "natural moisturizing factor," which helps maintain hydration of the outermost layer of skin.  Mutations in the FLG gene lead to production of an abnormally short profilaggrin molecule that cannot be cleaved to produce filaggrin proteins. The resulting shortage of filaggrin can impair the barrier function of the skin. In addition, a lack of natural moisturizing factor allows excess water loss through the skin, which can lead to dry skin.  Research shows that impairment of the skin's barrier function contributes to development of allergic disorders. An allergic reaction occurs when the body mistakenly recognizes a harmless substance, such as pollen, as a danger and stimulates an immune response to it. Research suggests that without a properly functioning barrier, allergens are able to get into the body through the skin. For unknown reasons, in susceptible individuals the body reacts as if the allergen is harmful and produces immune proteins called IgE antibodies specific to the allergen. Upon later encounters with the allergen, IgE antibodies recognize it, which stimulates an immune response, causing the symptoms of allergies, such as itchy, watery eyes or breathing difficulty. Although atopic dermatitis is not initially caused by an allergic reaction, flare-ups of the rashes can be triggered by allergens. The impaired barrier function caused by FLG gene mutations also contributes to the increased risk of asthma and other allergic disorders in people with atopic dermatitis.  Mutations in many other genes, most of which have not been identified, are likely associated with development of atopic dermatitis. Researchers suspect these genes are involved in the skin's barrier function or in the function of the immune system. However, not everyone with a mutation in FLG or another associated gene develops atopic dermatitis; exposure to certain environmental factors also contributes to the development of the disorder. Studies suggest that these exposures trigger epigenetic changes to the DNA. Epigenetic changes modify DNA without changing the DNA sequence. They can affect gene activity and regulate the production of proteins, which may influence the development of allergies in susceptible individuals. </s>


Input: Is atopic dermatitis inherited ?

Output: Allergic disorders tend to run in families; having a parent with atopic dermatitis, asthma, or hay fever raises the chances a person will develop atopic dermatitis. When associated with FLG gene mutations, atopic dermatitis follows an autosomal dominant inheritance pattern, which means one copy of the altered FLG gene in each cell is sufficient to increase the risk of the disorder. Individuals with two altered copies of the gene are more likely to develop the disorder and can have more severe signs and symptoms than individuals with a single altered copy. When associated with other genetic factors, the inheritance pattern is unclear.  People with changes in one of the genes associated with atopic dermatitis, including FLG, inherit an increased risk of this condition, not the condition itself. Not all people with this condition have a mutation in an associated gene, and not all people with a variation in an associated gene will develop the disorder. </s>


Input: What are the treatments for atopic dermatitis ?

Output: These resources address the diagnosis or management of atopic dermatitis:  - American Academy of Dermatology: Atopic Dermatitis: Tips for Managing   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) renal hypouricemia ?

Output: Renal hypouricemia is a kidney (renal) disorder that results in a reduced amount of uric acid in the blood. Uric acid is a byproduct of certain normal chemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. However, having too much uric acid in the body is toxic, so excess uric acid is removed from the body in urine.  People with renal hypouricemia have little to no uric acid in their blood; they release an excessive amount of it in the urine. In many affected individuals, renal hypouricemia causes no signs or symptoms. However, some people with this condition develop kidney problems. After strenuous exercise, they can develop exercise-induced acute kidney injury, which causes pain in their sides and lower back as well as nausea and vomiting that can last several hours.  Because an excessive amount of uric acid passes through the kidneys to be excreted in urine in people with renal hypouricemia, they have an increased risk of developing kidney stones (nephrolithiasis) formed from uric acid crystals. These uric acid stones can damage the kidneys and lead to episodes of blood in the urine (hematuria). Rarely, people with renal hypouricemia develop life-threatening kidney failure. </s>


Input: How many people are affected by renal hypouricemia ?

Output: The prevalence of renal hypouricemia is unknown; at least 150 affected individuals have been described in the scientific literature. This condition is thought to be most prevalent in Asian countries such as Japan and South Korea, although affected individuals have been found in Europe. Renal hypouricemia is likely underdiagnosed because it does not cause any symptoms in many affected individuals. </s>


Input: What are the genetic changes related to renal hypouricemia ?

Output: Mutations in the SLC22A12 or SLC2A9 gene cause renal hypouricemia. These genes provide instructions for making proteins called urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), respectively. These proteins are found in the kidneys, specifically in structures called proximal tubules. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete unneeded substances into the urine. Within the proximal tubules, both the URAT1 and GLUT9 proteins reabsorb uric acid into the bloodstream or release it into the urine, depending on the body's needs. Most uric acid that is filtered through the kidneys is reabsorbed into the bloodstream; about 10 percent is released into urine.  Mutations that cause renal hypouricemia lead to the production of URAT1 or GLUT9 protein with a reduced ability to reabsorb uric acid into the bloodstream. Instead, large amounts of uric acid are released in the urine. The specific cause of the signs and symptoms of renal hypouricemia is unclear. Researchers suspect that when additional uric acid is produced during exercise and passed through the kidneys, it could lead to tissue damage. Alternatively, without the antioxidant properties of uric acid, free radicals could cause tissue damage in the kidneys. Another possibility is that other substances are prevented from being reabsorbed along with uric acid; accumulation of these substances in the kidneys could cause tissue damage. It is likely that individuals with renal hypouricemia who have mild or no symptoms have enough protein function to reabsorb a sufficient amount of uric acid into the bloodstream to prevent severe kidney problems. </s>


Input: Is renal hypouricemia inherited ?

Output: This condition is typically inherited in an autosomal recessive pattern, which means both copies of the SLC22A12 or SLC2A9 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 usually do not show signs and symptoms of the condition.  Sometimes, individuals with one SLC2A9 gene mutation in each cell have reduced levels of uric acid. The levels usually are not as low as they are in people who have mutations in both copies of the gene, and they often do not cause any signs or symptoms. Rarely, people who carry one copy of the mutated gene will develop uric acid kidney stones. </s>


Input: What are the treatments for renal hypouricemia ?

Output: These resources address the diagnosis or management of renal hypouricemia:  - Genetic Testing Registry: Familial renal hypouricemia  - Genetic Testing Registry: Renal hypouricemia 2  - KidsHealth from Nemours: Blood Test: Uric Acid  - MedlinePlus Encyclopedia: Uric Acid--Blood   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) 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?

Output: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are used for energy during periods without food (fasting).  The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia). During an episode, blood sugar levels can become dangerously low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress.  HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. </s>


Input: How many people are affected by 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?

Output: HMG-CoA lyase deficiency is a rare condition; it has been reported in fewer than 100 individuals worldwide. Most people diagnosed with this disorder have been from Saudi Arabia, Portugal, or Spain. </s>


Input: What are the genetic changes related to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?

Output: Mutations in the HMGCL gene cause HMG-CoA lyase deficiency. The HMGCL gene provides instructions for making an enzyme known as 3-hydroxymethyl-3-methylglutaryl-coenzyme A lyase (HMG-CoA lyase). This enzyme plays a critical role in breaking down dietary proteins and fats for energy. Specifically, it is responsible for processing leucine, an amino acid that is part of many proteins. HMG-CoA lyase also produces ketones during the breakdown of fats. Ketones are compounds that certain organs and tissues, particularly the brain, use for energy when the simple sugar glucose is not available. For example, ketones are important sources of energy during periods of fasting.  If a mutation in the HMGCL gene reduces or eliminates the activity of HMG-CoA lyase, the body is unable to process leucine or make ketones properly. When leucine is not processed normally, a buildup of chemical byproducts called organic acids can result in metabolic acidosis. A shortage of ketones often leads to hypoglycemia. Metabolic acidosis and hypoglycemia can damage cells, particularly in the brain, resulting in serious illness in children with HMG-CoA lyase deficiency. </s>


Input: Is 3-hydroxy-3-methylglutaryl-CoA lyase 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 3-hydroxy-3-methylglutaryl-CoA lyase deficiency ?

Output: These resources address the diagnosis or management of HMG-CoA lyase deficiency:  - Baby's First Test  - Genetic Testing Registry: Deficiency of hydroxymethylglutaryl-CoA lyase   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) Poland syndrome ?

Output: Poland syndrome is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals.  People with Poland syndrome are typically missing part of one of the major chest muscles, called the pectoralis major. In most affected individuals, the missing part is the large section of the muscle that normally runs from the upper arm to the breastbone (sternum). The abnormal pectoralis major muscle may cause the chest to appear concave. In some cases, additional muscles on the affected side of the torso, including muscles in the chest wall, side, and shoulder, may be missing or underdeveloped. There may also be rib cage abnormalities, such as shortened ribs, and the ribs may be noticeable due to less fat under the skin (subcutaneous fat). Breast and nipple abnormalities may also occur, and underarm (axillary) hair is sometimes sparse or abnormally placed. In most cases, the abnormalities in the chest area do not cause health problems or affect movement.  Many people with Poland syndrome have hand abnormalities on the affected side, commonly including an underdeveloped hand with abnormally short fingers (brachydactyly); small, underdeveloped (vestigial) fingers; and some fingers that are fused together (syndactyly). This combination of hand abnormalities is called symbrachydactyly. Some affected individuals have only one or two of these features, or have a mild hand abnormality that is hardly noticeable; more severe abnormalities can cause problems with use of the hand. The bones of the forearm (radius and ulna) are shortened in some people with Poland syndrome, but this shortening may also be difficult to detect unless measured.  Mild cases of Poland syndrome without hand involvement may not be evident until puberty, when the differences (asymmetry) between the two sides of the chest become more apparent. By contrast, severely affected individuals have abnormalities of the chest, hand, or both that are apparent at birth. In rare cases, severely affected individuals have abnormalities of internal organs such as a lung or a kidney, or the heart is abnormally located in the right side of the chest (dextrocardia).  Rarely, chest and hand abnormalities resembling those of Poland syndrome occur on both sides of the body, but researchers disagree as to whether this condition is a variant of Poland syndrome or a different disorder. </s>


Input: How many people are affected by Poland syndrome ?

Output: Poland syndrome has been estimated to occur in 1 in 20,000 newborns. For unknown reasons, this disorder occurs more than twice as often in males than in females. Poland syndrome may be underdiagnosed because mild cases without hand involvement may never come to medical attention. </s>


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

Output: The cause of Poland syndrome is unknown. Researchers have suggested that it may result from a disruption of blood flow during development before birth. This disruption is thought to occur at about the sixth week of embryonic development and affect blood vessels that will become the subclavian and vertebral arteries on each side of the body. The arteries normally supply blood to embryonic tissues that give rise to the chest wall and hand on their respective sides. Variations in the site and extent of the disruption may explain the range of signs and symptoms that occur in Poland syndrome. Abnormality of an embryonic structure called the apical ectodermal ridge, which helps direct early limb development, may also be involved in this disorder.  Rare cases of Poland syndrome are thought to be caused by a genetic change that can be passed down in families, but no related genes have been identified. </s>


Input: Is Poland syndrome inherited ?

Output: Most cases of Poland syndrome are sporadic, which means they are not inherited and occur in people with no history of the disorder in their families. Rarely, this condition is passed through generations in families. In these families the condition appears to be inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder, although no associated genes have been found. </s>


Input: What are the treatments for Poland syndrome ?

Output: These resources address the diagnosis or management of Poland syndrome:  - Children's Medical Center of Dallas  - Great Ormond Street Hospital (UK): Treatment Options for Symbrachydactyly  - St. Louis Children's Hospital: Chest Wall Deformities   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) myopathy with deficiency of iron-sulfur cluster assembly enzyme ?

Output: Myopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles used for movement (skeletal muscles). This condition does not usually affect other types of muscle, such as the heart (cardiac) muscle.  From early childhood, affected individuals experience extreme fatigue in response to physical activity (exercise intolerance). Mild exertion results in a rapid heartbeat (tachycardia), shortness of breath, and muscle weakness and pain. However, people with this condition typically have normal muscle strength when they are at rest.  Prolonged or recurrent physical activity causes more severe signs and symptoms, including a breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure.  In most affected individuals, the muscle problems associated with this condition do not worsen with time. However, at least two people with a severe variant of this disorder have experienced progressive muscle weakness and wasting starting in childhood. </s>


Input: How many people are affected by myopathy with deficiency of iron-sulfur cluster assembly enzyme ?

Output: This condition has been reported in several families of northern Swedish ancestry. </s>


Input: What are the genetic changes related to myopathy with deficiency of iron-sulfur cluster assembly enzyme ?

Output: Myopathy with deficiency of iron-sulfur cluster assembly enzyme is caused by mutations in the ISCU gene. This gene provides instructions for making a protein called the iron-sulfur cluster assembly enzyme. As its name suggests, this enzyme is involved in the formation of clusters of iron and sulfur atoms (Fe-S clusters). These clusters are critical for the function of many different proteins, including those needed for DNA repair and the regulation of iron levels. Proteins containing Fe-S clusters are also necessary for energy production within mitochondria, which are the cell structures that convert the energy from food into a form that cells can use.  Mutations in the ISCU gene severely limit the amount of iron-sulfur cluster assembly enzyme that is made in cells. A shortage of this enzyme prevents the normal production of proteins that contain Fe-S clusters, which disrupts a variety of cellular activities. A reduction in the amount of iron-sulfur cluster assembly enzyme is particularly damaging to skeletal muscle cells. Within the mitochondria of these cells, a lack of this enzyme causes problems with energy production and an overload of iron. These defects lead to exercise intolerance and the other features of myopathy with deficiency of iron-sulfur cluster assembly enzyme. </s>


Input: Is myopathy with deficiency of iron-sulfur cluster assembly enzyme 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 myopathy with deficiency of iron-sulfur cluster assembly enzyme ?

Output: These resources address the diagnosis or management of myopathy with deficiency of iron-sulfur cluster assembly enzyme:  - Gene Review: Gene Review: Myopathy with Deficiency of ISCU  - Genetic Testing Registry: Myopathy with lactic acidosis, hereditary  - MedlinePlus Encyclopedia: Rhabdomyolysis   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) dyskeratosis congenita ?

Output: Dyskeratosis congenita is a disorder that can affect many parts of the body. There are three features that are characteristic of this disorder: fingernails and toenails that grow poorly or are abnormally shaped (nail dystrophy); changes in skin coloring (pigmentation), especially on the neck and chest, in a pattern often described as "lacy"; and white patches inside the mouth (oral leukoplakia).  People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions. They are especially vulnerable to disorders that impair bone marrow function. These disorders disrupt the ability of the bone marrow to produce new blood cells. Affected individuals may develop aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells. They are also at higher than average risk for myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally; this condition may progress to a form of blood cancer called leukemia. People with dyskeratosis congenita are also at increased risk of developing leukemia even if they never develop myelodysplastic syndrome. In addition, they have a higher than average risk of developing other cancers, especially cancers of the head, neck, anus, or genitals.  People with dyskeratosis congenita may also develop pulmonary fibrosis, a condition that causes scar tissue (fibrosis) to build up in the lungs, decreasing the transport of oxygen into the bloodstream. Additional signs and symptoms that occur in some people with dyskeratosis congenita include eye abnormalities such as narrow tear ducts that may become blocked, preventing drainage of tears and leading to eyelid irritation; dental problems; hair loss or prematurely grey hair; low bone mineral density (osteoporosis); degeneration (avascular necrosis) of the hip and shoulder joints; or liver disease. Some affected males may have narrowing (stenosis) of the urethra, which is the tube that carries urine out of the body from the bladder. Urethral stenosis may lead to difficult or painful urination and urinary tract infections.  The severity of dyskeratosis congenita varies widely among affected individuals. The least severely affected individuals have only a few mild physical features of the disorder and normal bone marrow function. More severely affected individuals have many of the characteristic physical features and experience bone marrow failure, cancer, or pulmonary fibrosis by early adulthood.  While most people with dyskeratosis congenita have normal intelligence and development of motor skills such as standing and walking, developmental delay may occur in some severely affected individuals. In one severe form of the disorder called Hoyeraal Hreidaarsson syndrome, affected individuals have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. Another severe variant called Revesz syndrome involves abnormalities in the light-sensitive tissue at the back of the eye (retina) in addition to the other symptoms of dyskeratosis congenita. </s>


Input: How many people are affected by dyskeratosis congenita ?

Output: The exact prevalence of dyskeratosis congenita is unknown. It is estimated to occur in approximately 1 in 1 million people. </s>


Input: What are the genetic changes related to dyskeratosis congenita ?

Output: In about half of people with dyskeratosis congenita, the disorder is caused by mutations in the TERT, TERC, DKC1, or TINF2 gene. These genes provide instructions for making proteins that help maintain structures known as telomeres, which are found at the ends of chromosomes. In a small number of individuals with dyskeratosis congenita, mutations in other genes involved with telomere maintenance have been identified. Other affected individuals have no mutations in any of the genes currently associated with dyskeratosis congenita. In these cases, the cause of the disorder is unknown, but other unidentified genes related to telomere maintenance are likely involved.  Telomeres help protect chromosomes from abnormally sticking together or breaking down (degrading). In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis).  Telomeres are maintained by two important protein complexes called telomerase and shelterin. Telomerase helps maintain normal telomere length by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides. The main components of telomerase, called hTR and hTERT, are produced from the TERC and TERT genes, respectively. The hTR component is an RNA molecule, a chemical cousin of DNA. It provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. The function of the hTERT component is to add the new DNA segment to chromosome ends. The DKC1 gene provides instructions for making another protein that is important in telomerase function. This protein, called dyskerin, attaches (binds) to hTR and helps stabilize the telomerase complex.  The shelterin complex helps protect telomeres from the cell's DNA repair process. Without the protection of shelterin, the repair mechanism would sense the chromosome ends as abnormal breaks in the DNA sequence and either attempt to join the ends together or initiate apoptosis. The TINF2 gene provides instructions for making a protein that is part of the shelterin complex.  TERT, TERC, DKC1, or TINF2 gene mutations result in dysfunction of the telomerase or shelterin complexes, leading to impaired maintenance of telomeres and reduced telomere length. Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. As a result, people with dyskeratosis congenita may experience a variety of problems affecting quickly dividing cells in the body such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow.  Breakage and instability of chromosomes resulting from inadequate telomere maintenance may lead to genetic changes that allow cells to divide in an uncontrolled way, resulting in the development of cancer in people with dyskeratosis congenita. </s>


Input: Is dyskeratosis congenita inherited ?

Output: Dyskeratosis congenita can have different inheritance patterns.  When dyskeratosis congenita is caused by DKC1 gene mutations, it is inherited in an X-linked recessive pattern. The DKC1 gene 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. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.  When dyskeratosis congenita is caused by mutations in other genes, it can be inherited in an autosomal dominant or autosomal recessive pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder. Autosomal recessive 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 dyskeratosis congenita ?

Output: These resources address the diagnosis or management of dyskeratosis congenita:  - Gene Review: Gene Review: Dyskeratosis Congenita  - Genetic Testing Registry: Dyskeratosis congenita  - Genetic Testing Registry: Dyskeratosis congenita X-linked  - Genetic Testing Registry: Dyskeratosis congenita autosomal dominant  - Genetic Testing Registry: Dyskeratosis congenita autosomal recessive 1  - Seattle Children's Hospital   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 spherocytosis ?

Output: Hereditary spherocytosis is a condition that affects red blood cells. People with this condition typically experience a shortage of red blood cells (anemia), yellowing of the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe anemia, although it improves after the first year of life. Splenomegaly can occur anytime from early childhood to adulthood. About half of affected individuals develop hard deposits in the gallbladder called gallstones, which typically occur from late childhood to mid-adulthood.  There are four forms of hereditary spherocytosis, which are distinguished by the severity of signs and symptoms. They are known as the mild form, the moderate form, the moderate/severe form, and the severe form. It is estimated that 20 to 30 percent of people with hereditary spherocytosis have the mild form, 60 to 70 percent have the moderate form, 10 percent have the moderate/severe form, and 3 to 5 percent have the severe form.  People with the mild form may have very mild anemia or sometimes have no symptoms. People with the moderate form typically have anemia, jaundice, and splenomegaly. Many also develop gallstones. The signs and symptoms of moderate hereditary spherocytosis usually appear in childhood. Individuals with the moderate/severe form have all the features of the moderate form but also have severe anemia. Those with the severe form have life-threatening anemia that requires frequent blood transfusions to replenish their red blood cell supply. They also have severe splenomegaly, jaundice, and a high risk for developing gallstones. Some individuals with the severe form have short stature, delayed sexual development, and skeletal abnormalities. </s>


Input: How many people are affected by hereditary spherocytosis ?

Output: Hereditary spherocytosis occurs in 1 in 2,000 individuals of Northern European ancestry. This condition is the most common cause of inherited anemia in that population. The prevalence of hereditary spherocytosis in people of other ethnic backgrounds is unknown, but it is much less common. </s>


Input: What are the genetic changes related to hereditary spherocytosis ?

Output: Mutations in at least five genes cause hereditary spherocytosis. These genes provide instructions for producing proteins that are found on the membranes of red blood cells. These proteins transport molecules into and out of cells, attach to other proteins, and maintain cell structure. Some of these proteins allow for cell flexibility; red blood cells have to be flexible to travel from the large blood vessels (arteries) to the smaller blood vessels (capillaries). The proteins allow the cell to change shape without breaking when passing through narrow capillaries.  Mutations in red blood cell membrane proteins result in an overly rigid, misshapen cell. Instead of a flattened disc shape, these cells are spherical. Dysfunctional membrane proteins interfere with the cell's ability to change shape when traveling through the blood vessels. The misshapen red blood cells, called spherocytes, are removed from circulation and taken to the spleen for destruction. Within the spleen, the red blood cells break down (undergo hemolysis). The shortage of red blood cells in circulation and the abundance of cells in the spleen are responsible for the signs and symptoms of hereditary spherocytosis.  Mutations in the ANK1 gene are responsible for approximately half of all cases of hereditary spherocytosis. The other genes associated with hereditary spherocytosis each account for a smaller percentage of cases of this condition. </s>


Input: Is hereditary spherocytosis inherited ?

Output: In about 75 percent of cases, hereditary spherocytosis is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, 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.  This condition can also be 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 hereditary spherocytosis ?

Output: These resources address the diagnosis or management of hereditary spherocytosis:  - Genetic Testing Registry: Hereditary spherocytosis  - Genetic Testing Registry: Spherocytosis type 2  - Genetic Testing Registry: Spherocytosis type 3  - Genetic Testing Registry: Spherocytosis type 4  - Genetic Testing Registry: Spherocytosis type 5  - Genetic Testing Registry: Spherocytosis, type 1, autosomal recessive  - Seattle Children's Hospital: Hereditary Spherocytosis Treatment Options   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) achondrogenesis ?

Output: Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. However, some infants have lived for a short time with intensive medical support.  Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. However, types 1A and 1B are often hard to tell apart without genetic testing.  Achondrogenesis type 1A, which is also called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis.  Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may turn inward and upward (clubfeet). Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia).  Infants with achondrogenesis type 2, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis, in which excess fluid builds up in the body before birth. </s>


Input: How many people are affected by achondrogenesis ?

Output: Achondrogenesis types 1A and 1B are rare genetic disorders; their incidence is unknown. Combined, achondrogenesis type 2 and hypochondrogenesis (a similar skeletal disorder) occur in 1 in 40,000 to 60,000 newborns. </s>


Input: What are the genetic changes related to achondrogenesis ?

Output: Mutations in the TRIP11, SLC26A2, and COL2A1 genes cause achondrogenesis type 1A, type 1B, and type 2, respectively.  The genetic cause of achondrogenesis type 1A was unknown until recently, when researchers discovered that the condition can result from mutations in the TRIP11 gene. This gene provides instructions for making a protein called GMAP-210. This protein plays a critical role in the Golgi apparatus, a cell structure in which newly produced proteins are modified so they can carry out their functions. Mutations in the TRIP11 gene prevent the production of functional GMAP-210, which alters the structure and function of the Golgi apparatus. Researchers suspect that cells called chondrocytes in the developing skeleton may be most sensitive to these changes. Chondrocytes give rise to cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Malfunction of the Golgi apparatus in chondrocytes likely underlies the problems with bone formation in achondrogenesis type 1A.  Achondrogenesis type 1B is the most severe of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Mutations in the SLC26A2 gene cause the skeletal problems characteristic of achondrogenesis type 1B by disrupting the structure of developing cartilage, which prevents bones from forming properly.  Achondrogenesis type 2 is one of several skeletal disorders that result from mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). It is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly. </s>


Input: Is achondrogenesis inherited ?

Output: Achondrogenesis type 1A and type 1B both have an autosomal recessive pattern of inheritance, which means both copies of the TRIP11 or SLC26A2 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition.  Achondrogenesis type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is almost always caused by new mutations in the COL2A1 gene and typically occurs in people with no history of the disorder in their family. </s>


Input: What are the treatments for achondrogenesis ?

Output: These resources address the diagnosis or management of achondrogenesis:  - Gene Review: Gene Review: Achondrogenesis Type 1B  - Genetic Testing Registry: Achondrogenesis type 2  - Genetic Testing Registry: Achondrogenesis, type IA  - Genetic Testing Registry: Achondrogenesis, type IB  - MedlinePlus Encyclopedia: Achondrogenesis   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) rhizomelic chondrodysplasia punctata ?

Output: Rhizomelic chondrodysplasia punctata is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems.  Rhizomelic chondrodysplasia punctata is characterized by shortening of the bones in the upper arms and thighs (rhizomelia). Affected individuals also have a specific bone abnormality called chondrodysplasia punctata, which affects the growth of the long bones and can be seen on x-rays. People with rhizomelic chondrodysplasia punctata often develop joint deformities (contractures) that make the joints stiff and painful.  Distinctive facial features are also seen with rhizomelic chondrodysplasia punctata. These include a prominent forehead, widely set eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), a small nose with upturned nostrils, and full cheeks. Additionally, almost all affected individuals have clouding of the lenses of the eyes (cataracts). The cataracts are apparent at birth (congenital) or develop in early infancy.  Rhizomelic chondrodysplasia punctata is associated with significantly delayed development and severe intellectual disability. Most children with this condition do not achieve developmental milestones such as sitting without support, feeding themselves, or speaking in phrases. Affected infants grow much more slowly than other children their age, and many also have seizures. Recurrent respiratory infections and life-threatening breathing problems are common. Because of their severe health problems, most people with rhizomelic chondrodysplasia punctata survive only into childhood. It is rare for affected children to live past age 10. However, a few individuals with milder features of the condition have lived into early adulthood.  Researchers have described three types of rhizomelic chondrodysplasia punctata: type 1 (RCDP1), type 2 (RCDP2), and type 3 (RCDP3). The types have similar features and are distinguished by their genetic cause. </s>


Input: How many people are affected by rhizomelic chondrodysplasia punctata ?

Output: Rhizomelic chondrodysplasia punctata affects fewer than 1 in 100,000 people worldwide. RCDP1 is more common than RCDP2 or RCDP3. </s>


Input: What are the genetic changes related to rhizomelic chondrodysplasia punctata ?

Output: Rhizomelic chondrodysplasia punctata results from mutations in one of three genes. Mutations in the PEX7 gene, which are most common, cause RCDP1. Changes in the GNPAT gene lead to RCDP2, while AGPS gene mutations result in RCDP3.  The genes associated with rhizomelic chondrodysplasia punctata are involved in the formation and function of structures called peroxisomes. Peroxisomes are sac-like compartments within cells that contain enzymes needed to break down many different substances, including fatty acids and certain toxic compounds. They are also important for the production of fats (lipids) used in digestion and in the nervous system.  Within peroxisomes, the proteins produced from the PEX7, GNPAT, and AGPS genes play roles in the formation (synthesis) of lipid molecules called plasmalogens. Plasmalogens are found in cell membranes throughout the body, although little is known about their function. Mutations in the PEX7, GNPAT, or AGPS genes prevent peroxisomes from making plasmalogens. Researchers are working to determine how problems with plasmalogen synthesis lead to the specific signs and symptoms of rhizomelic chondrodysplasia punctata. </s>


Input: Is rhizomelic chondrodysplasia punctata 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 rhizomelic chondrodysplasia punctata ?

Output: These resources address the diagnosis or management of rhizomelic chondrodysplasia punctata:  - Gene Review: Gene Review: Rhizomelic Chondrodysplasia Punctata Type 1  - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 1  - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 2  - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 3   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) lactose intolerance ?

Output: Lactose intolerance is an impaired ability to digest lactose, a sugar found in milk and other dairy products. Lactose is normally broken down by an enzyme called lactase, which is produced by cells in the lining of the small intestine.  Congenital lactase deficiency, also called congenital alactasia, is a disorder in which infants are unable to break down lactose in breast milk or formula. This form of lactose intolerance results in severe diarrhea. If affected infants are not given a lactose-free infant formula, they may develop severe dehydration and weight loss.  Lactose intolerance in adulthood is caused by reduced production of lactase after infancy (lactase nonpersistence). If individuals with lactose intolerance consume lactose-containing dairy products, they may experience abdominal pain, bloating, flatulence, nausea, and diarrhea beginning 30 minutes to 2 hours later.  Most people with lactase nonpersistence retain some lactase activity and can include varying amounts of lactose in their diets without experiencing symptoms. Often, affected individuals have difficulty digesting fresh milk but can eat certain dairy products such as cheese or yogurt without discomfort. These foods are made using fermentation processes that break down much of the lactose in milk. </s>


Input: How many people are affected by lactose intolerance ?

Output: Lactose intolerance in infancy resulting from congenital lactase deficiency is a rare disorder. Its incidence is unknown. This condition is most common in Finland, where it affects an estimated 1 in 60,000 newborns.  Approximately 65 percent of the human population has a reduced ability to digest lactose after infancy. Lactose intolerance in adulthood is most prevalent in people of East Asian descent, affecting more than 90 percent of adults in some of these communities. Lactose intolerance is also very common in people of West African, Arab, Jewish, Greek, and Italian descent.  The prevalence of lactose intolerance is lowest in populations with a long history of dependence on unfermented milk products as an important food source. For example, only about 5 percent of people of Northern European descent are lactose intolerant. </s>


Input: What are the genetic changes related to lactose intolerance ?

Output: Lactose intolerance in infants (congenital lactase deficiency) is caused by mutations in the LCT gene. The LCT gene provides instructions for making the lactase enzyme. Mutations that cause congenital lactase deficiency are believed to interfere with the function of lactase, causing affected infants to have a severely impaired ability to digest lactose in breast milk or formula.  Lactose intolerance in adulthood is caused by gradually decreasing activity (expression) of the LCT gene after infancy, which occurs in most humans. LCT gene expression is controlled by a DNA sequence called a regulatory element, which is located within a nearby gene called MCM6. Some individuals have inherited changes in this element that lead to sustained lactase production in the small intestine and the ability to digest lactose throughout life. People without these changes have a reduced ability to digest lactose as they get older, resulting in the signs and symptoms of lactose intolerance. </s>


Input: Is lactose intolerance inherited ?

Output: The type of lactose intolerance that occurs in infants (congenital lactase deficiency) is inherited in an autosomal recessive pattern, which means both copies of the LCT 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.  The ability to digest lactose into adulthood depends on which variations in the regulatory element within the MCM6 gene individuals have inherited from their parents. The variations that promote continued lactase production are considered autosomal dominant, which means one copy of the altered regulatory element in each cell is sufficient to sustain lactase production. People who have not inherited these variations from either parent will have some degree of lactose intolerance. </s>


Input: What are the treatments for lactose intolerance ?

Output: These resources address the diagnosis or management of lactose intolerance:  - Genetic Testing Registry: Congenital lactase deficiency  - Genetic Testing Registry: Nonpersistence of intestinal lactase  - MedlinePlus Encyclopedia: Lactose Intolerance  - MedlinePlus Encyclopedia: Lactose Tolerance 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) spinocerebellar ataxia type 2 ?

Output: Spinocerebellar ataxia type 2 (SCA2) is a condition characterized by progressive problems with movement. People with this condition initially experience problems with coordination and balance (ataxia). Other early signs and symptoms of SCA2 include speech and swallowing difficulties, rigidity, tremors, and weakness in the muscles that control eye movement (ophthalmoplegia). Eye muscle weakness leads to a decreased ability to make rapid eye movements (saccadic slowing).  Over time, individuals with SCA2 may develop loss of sensation and weakness in the limbs (peripheral neuropathy), muscle wasting (atrophy), uncontrolled muscle tensing (dystonia), and involuntary jerking movements (chorea). Individuals with SCA2 may have problems with short term memory, planning, and problem solving, or experience an overall decline in intellectual function (dementia).  Signs and symptoms of the disorder typically begin in mid-adulthood but can appear anytime from childhood to late adulthood. People with SCA2 usually survive 10 to 20 years after symptoms first appear. </s>


Input: How many people are affected by spinocerebellar ataxia type 2 ?

Output: The prevalence of SCA2 is unknown. This condition is estimated to be one of the most common types of spinocerebellar ataxia; however, all types of spinocerebellar ataxia are relatively rare. SCA2 is more common in Cuba, particularly in the Holgun province, where approximately 40 per 100,000 individuals are affected. </s>


Input: What are the genetic changes related to spinocerebellar ataxia type 2 ?

Output: Mutations in the ATXN2 gene cause SCA2. The ATXN2 gene provides instructions for making a protein called ataxin-2. This protein is found throughout the body, but its function is unknown. Ataxin-2 is found in the fluid inside cells (cytoplasm), where it appears to interact with a cell structure called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Researchers believe that ataxin-2 may be involved in processing RNA, a chemical cousin of DNA. Ataxin-2 is also thought to play a role in the production of proteins from RNA (translation of DNA's genetic information).  The ATXN2 gene mutations that cause SCA2 involve a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated approximately 22 times within the gene, but it can be repeated up to 31 times without causing any health problems. Individuals with 32 or more CAG repeats in the ATXN2 gene develop SCA2. People with 32 or 33 repeats tend to first experience signs and symptoms of SCA2 in late adulthood, while people with more than 45 repeats usually have signs and symptoms by their teens.  It is unclear how the abnormally long CAG segment affects the function of the ataxin-2 protein. The abnormal protein apparently leads to cell death, as people with SCA2 show loss of brain cells in different parts of the brain. Over time, the loss of brain cells causes the movement problems characteristic of SCA2. </s>


Input: Is spinocerebellar ataxia type 2 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. An affected person usually inherits the altered gene from one affected parent. However, some people with SCA2 do not have a parent with the disorder. Individuals who have an increase in the number of CAG repeats in the ATXN2 gene, but do not develop SCA2, are at risk of having children who will develop the disorder.  As the altered ATXN2 gene is passed down from one generation to the next, the length of the CAG trinucleotide repeat often increases. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. Anticipation tends to be more prominent when the ATXN2 gene is inherited from a person's father (paternal inheritance) than when it is inherited from a person's mother (maternal inheritance). </s>


Input: What are the treatments for spinocerebellar ataxia type 2 ?

Output: These resources address the diagnosis or management of SCA2:  - Gene Review: Gene Review: Spinocerebellar Ataxia Type 2  - Genetic Testing Registry: Spinocerebellar ataxia 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) beta-ureidopropionase deficiency ?

Output: Beta-ureidopropionase deficiency is a disorder that causes excessive amounts of molecules called N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine to be released in the urine. Neurological problems ranging from mild to severe also occur in some affected individuals.  People with beta-ureidopropionase deficiency can have low muscle tone (hypotonia), seizures, speech difficulties, developmental delay, intellectual disability, and autistic behaviors that affect communication and social interaction. Some people with this condition have an abnormally small head size (microcephaly); they may also have brain abnormalities that can be seen with medical imaging. Deterioration of the optic nerve, which carries visual information from the eyes to the brain, can lead to vision loss in this condition.  In some people with beta-ureidopropionase deficiency, the disease causes no neurological problems and can only be diagnosed by laboratory testing. </s>


Input: How many people are affected by beta-ureidopropionase deficiency ?

Output: The prevalence of beta-ureidopropionase deficiency is unknown. A small number of affected individuals from populations around the world have been described in the medical literature. In Japan, the prevalence of beta-ureidopropionase deficiency has been estimated as 1 in 6,000 people. Researchers suggest that in many affected individuals with absent or mild neurological problems, the condition may never be diagnosed. </s>


Input: What are the genetic changes related to beta-ureidopropionase deficiency ?

Output: Beta-ureidopropionase deficiency is caused by mutations in the UPB1 gene, which provides instructions for making an enzyme called beta-ureidopropionase. This enzyme is involved in the breakdown of molecules called pyrimidines, which are building blocks of DNA and its chemical cousin RNA.  The beta-ureidopropionase enzyme is involved in the last step of the process that breaks down pyrimidines. This step converts N-carbamyl-beta-aminoisobutyric acid to beta-aminoisobutyric acid and also breaks down N-carbamyl-beta-alanine to beta-alanine, ammonia, and carbon dioxide. Both beta-aminoisobutyric acid and beta-alanine are thought to play roles in the nervous system. Beta-aminoisobutyric acid increases the production of a protein called leptin, which has been found to help protect brain cells from damage caused by toxins, inflammation, and other factors. Research suggests that beta-alanine is involved in sending signals between nerve cells (synaptic transmission) and in controlling the level of a chemical messenger (neurotransmitter) called dopamine.  UPB1 gene mutations can reduce or eliminate beta-ureidopropionase enzyme activity. Loss of this enzyme function reduces the production of beta-aminoisobutyric acid and beta-alanine, and leads to an excess of their precursor molecules, N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine, which are released in the urine. Reduced production of beta-aminoisobutyric acid and beta-alanine may impair the function of these molecules in the nervous system, leading to neurological problems in some people with beta-ureidopropionase deficiency. The extent of the reduction in enzyme activity caused by a particular UPB1 gene mutation, along with other genetic and environmental factors, may determine whether people with beta-ureidopropionase deficiency develop neurological problems and the severity of these problems. </s>


Input: Is beta-ureidopropionase 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 beta-ureidopropionase deficiency ?

Output: These resources address the diagnosis or management of beta-ureidopropionase deficiency:  - Genetic Testing Registry: Deficiency of beta-ureidopropionase   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) microvillus inclusion disease ?

Output: Microvillus inclusion disease is a condition characterized by chronic, watery, life-threatening diarrhea typically beginning in the first hours to days of life. Rarely, the diarrhea starts around age 3 or 4 months. Food intake increases the frequency of diarrhea.  Microvillus inclusion disease prevents the absorption of nutrients from food during digestion, resulting in malnutrition and dehydration. Affected infants often have difficulty gaining weight and growing at the expected rate (failure to thrive), developmental delay, liver and kidney problems, and thinning of the bones (osteoporosis). Some affected individuals develop cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis).  In individuals with microvillus inclusion disease, lifelong nutritional support is needed and given through intravenous feedings (parenteral nutrition). Even with nutritional supplementation, most children with microvillus inclusion disease do not survive beyond childhood.  A variant of microvillus inclusion disease with milder diarrhea often does not require full-time parenteral nutrition. Individuals with the variant type frequently live past childhood. </s>


Input: How many people are affected by microvillus inclusion disease ?

Output: The prevalence of microvillus inclusion disease is unknown. At least 200 cases have been reported in Europe, although this condition occurs worldwide. </s>