question:  X-linked adrenoleukodystrophy X-ALD Adrenoleukodystrophy ALD Summary X-linked adrenoleukodystrophy (X-ALD) is a genetic disease that affects the nervous system and the adrenal glands (small glands located on top of each kidney). People with this disease often have progressive loss of the fatty covering ( myelin ) that surrounds the nerves in the brain and spinal cord. They may also have a shortage of certain hormones that is caused by damage to the outer layer of the adrenal glands (adrenal cortex). This is called adrenocortical insufficiency, or Addison disease. [1] There are three forms of X-ALD: a childhood cerebral form, an adrenomyeloneuropathy (AMN) type, and an adrenal-insufficiency-only-type. The disease primarily affects males. [1] X-ALD is caused by a variation ( mutation ) in the ABCD1 gene and it is inherited in an X-linked. manner. Diagnosis of the disease is based on testing the levels of a molecule called very long-chain fatty acids (VLCFA). The diagnosis can be confirmed with genetic testing . There is still no cure for X-ALD, but taking special oils such as Lorenzo's oil can lower the blood levels of VLCFA. Bone marrow transplantation may be an option for boys who have evidence of brain involvement on MRI but do not yet have obvious symptoms of the disease with a normal neurological exam. Adrenocortical insufficiency is treated with corticosteroids . [2] Symptoms X-linked adrenoleukodystrophy (X-ALD) symptoms are very varied. Basically there are three main types that are present in about 90% or 95% of the affected people: a childhood cerebral form or symptoms set 1, an adrenomyeloneuropathy (AMN) type or symptoms set 2, and an adrenal insufficiency-only type, or symptoms set 3. There are other other less common presentations (types) of the disease, known as symptoms sets 4 to 8: Childhood cerebral form of X-ALD (or symptoms set 1): It mostly present with neurological problems, and typically begin between ages 4-8 years-old. The first noticeable symptom is usually behavior problems in school such as struggling to pay attention. Some boys may have seizures as their first symptom. As the disease progresses, other symptoms may include vomiting, vision loss, learning disabilities, trouble eating ( dysphagia ), deafness, fatigue, and trouble coordinating movements ( ataxia ).[2][3] Adrenomyeloneuropathy (AMN) type (or symptoms set 2): Presents with both adrenal and neurological problems. It usually begin in early to mid-adulthood, and it is the most common presentation. Symptoms can include leg stiffness, weakness and pain in the hands and feet ( peripheral neuropathy ), muscle spasms and weakness, and urinary problems or sexual dysfunction.[2] Adrenal insufficiency-only (Addison disease-only) type (or symptoms set 3): It is characterized by adrenal insufficiency without neurologic problems. Symptoms of adrenal insufficiency can develop at any time between childhood and adulthood and include decreased appetite, increased pigment (melanin) in the skin making it appear darker, muscle weakness, and vomiting.[4] Symptoms seen in about 5%-10% of affected males may include: [2] Symptom set 4: Onset is between age four and ten years but may occur in adolescence or, rarely, in adults, and may include headache, increased intracranial pressure, paralysis of one side of the body (hemiparesis) or visual field defect, difficulty speaking or other signs of localized brain disease. Symptom set 5: Progressive behavioral disturbance, dementia , and paralysis in an adult Symptom set 6: Progressive lack of coordination in a child or adult Symptom set 7: Problems with urination and bowel abnormalities and occasionally impotence in at-risk males who have other affected relatives Symptom set 8. No evidence of neurologic or endocrine dysfunction Approximately 20% of female who are carriers develop mild to moderate weakness and spasticity (stiffness) of the legs (spastic paraparesis) in middle age or later. Adrenal function is usually normal. [2] This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom. Showing of Medical Terms Other Names Learn More: HPO ID 80%-99% of people have these symptoms Abnormality of metabolism/homeostasis Laboratory abnormality Metabolism abnormality 0001939 Attention deficit hyperactivity disorder Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder 0007018 Clumsiness 0002312 Dementia Dementia, progressive Progressive dementia 0000726 Functional motor deficit 0004302 Gait disturbance Abnormal gait Abnormal walk Impaired gait 0001288 Headache Headaches 0002315 Intellectual disability Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation 0001249 Leg muscle stiffness 0008969 Progressive hearing impairment 0001730 Progressive spastic paraparesis 0007199 Sensory impairment 0003474 Specific learning disability 0001328 Visual loss Loss of vision Vision loss 0000572 30%-79% of people have these symptoms Adrenal insufficiency 0000846 Aggressive behavior Aggression Aggressive behaviour Aggressiveness 0000718 Aphasia Difficulty finding words Losing words Loss of words 0002381 Disinhibition 0000734 Hemiparesis Weakness of one side of body 0001269 Inappropriate sexual behavior 0008768 Increased circulating ACTH level High blood corticotropin levels 0003154 Increased intracranial pressure Rise in pressure inside skull 0002516 Neurogenic bladder 0000011 Urinary bladder sphincter dysfunction 0002839 Visual field defect Partial loss of field of vision 0001123 5%-29% of people have these symptoms Diplopia Double vision 0000651 Impotence Difficulty getting a full erection Difficulty getting an erection Erectile dysfunction 0000802 Paralysis Inability to move 0003470 Percent of people who have these symptoms is not available through HPO Abnormality of the cerebral white matter 0002500 Abnormality of the skeletal system Skeletal abnormalities Skeletal anomalies 0000924 Blindness 0000618 Bowel incontinence Loss of bowel control 0002607 Bulbar palsy 0001283 Elevated long chain fatty acids 0003455 Hearing impairment Deafness Hearing defect 0000365 Hyperpigmentation of the skin Patchy darkened skin 0000953 Hypogonadism Decreased activity of gonads 0000135 Incoordination Difficulties in coordination Incoordination of limb movements Limb incoordination 0002311 Limb ataxia 0002070 Loss of speech 0002371 Neurodegeneration 0002180 Paraparesis 0002385 Polyneuropathy Peripheral nerve disease 0001271 Primary adrenal insufficiency 0008207 Progressive Worsens with time 0003676 Psychosis 0000709 Seizures Seizure 0001250 Slurred speech 0001350 Spastic paraplegia 0001258 Truncal ataxia 0002078 Urinary incontinence Loss of bladder control 0000020 X-linked inheritance 0001417 X-linked recessive inheritance 0001419 Showing of Cause X-linked adrenoleukodystrophy (X-ALD) is caused by a variation ( mutation ) in the ABCD1 gene. This gene provides instructions to make a protein called the adrenoleukodystrophy protein (ALDP). ALDP normally moves a type of fat molecule called very long-chain fatty acids (VLCFA) into a special part of the cell to be broken down. When the ABCD1 gene is changed, there is too little ALDP in the cells or the ALDP that is made does not work normally. This causes VLCFA to build up in the body. High levels of VLCFA are thought to be damaging to the outside of the adrenal glands (adrenal cortex) and the fatty covering ( myelin ) that surrounds the nerve cells in the brain and spinal cord. Researchers believe the damage caused by VLCFA may involve inflammation, especially in the brain. [1] [2] Inheritance X-linked adrenoleukodystrophy (X-ALD) is inherited in an X-linked manner. [1] This means that the ABCD1 gene is located on the X chromosome . The X chromosome is one of the sex chromosomes . Each woman has two X chromosomes, and each man has one X chromosome and one Y chromosome . Because men have only one X chromosome, they only have one copy of the ABCD1 gene. If this gene has a disease-causing change, they will have X-ALD. Women who have disease-causing changes in one copy of the ABCD1 gene are known as carriers of the disease. About 80% of carriers do not have signs or symptoms of X-ALD because they have another working copy of ABCD1. However, about 20% of female carriers have symptoms that are similar to the adrenomyeloneuropathy (AMN) type of X-ALD. [2] If a male is diagnosed with X-ALD, it is likely that his mother is a carrier of the disease. However, about 5% of cases of X-ALD are caused by a new genetic change ( de novo ) in the individual. In these situations, the mother is not a carrier of the disease, and other family members are not at risk to have children with X-ALD. Therefore, when a male is diagnosed with X-ALD, it is important to determine if his mother is a carrier by testing her VLCFA levels or by genetic testing . [2] If a woman is found to be a carrier of X-ALD, for each of her children there is a 50% chance that he or she will inherit the change in ABCD1. This means that for each son, there is a 50% chance that he will be affected with X-ALD. For each daughter, there is a 50% chance that she will be a carrier of the disease like her mother. X-ALD shows a characteristic known as variable expressivity. This means that the exact symptoms of each person with X-ALD can differ, even within the same family. For example, some boys may have the childhood cerebral form of X-ALD, while other members of the same family may have the adrenal insufficiency-only type. [2] It is not known what causes variable expressivity of the disease to occur. The symptoms cannot be predicted by levels of VLCFA or by looking at the exact genetic change ( mutation ) in each individual. [2] Diagnosis X-linked adrenoleukodystrophy (X-ALD) is suspected when a doctor observes signs and symptoms of the disease. X-ALD should be considered as a possible cause of symptoms in four situations: [2] Boys with attention deficit disorder (ADD) who also have signs of neurological problems Young men with progressive trouble walking or coordinating movements All males with adrenal insufficiency (Addison disease), even in the absence of other symptoms Adult women with progressive muscle weakness or wasting If a diagnosis of X-ALD is suspected, a blood test of very long-chain fatty acids will detect elevated levels in 99% of males. Genetic testing can be used to confirm the diagnosis. After diagnosis, a brain MRI can be completed to determine the extent of the disease. A brain MRI will be abnormal even if symptoms of the disease are not very severe. [2] Testing Resources The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Treatment The treatment for X-linked adrenoleukodystrophy (X-ALD) depends on the signs and symptoms present in each person and may include: [2] [5] Corticosteroids adrenal insufficiency Physical therapy adrenomyeloneuropathy (AMN) Bone marrow transplant brain MRI Lorenzo's oil Clinical trials investigating treatment with gene therapy are currently underway and have shown some preliminary success. [2] [6] Prognosis The long-term outlook for people affected by X-linked adrenoleukodystrophy (X-ALD) depends on the exact type of the disease that each person has. The childhood cerebral form of the disease is progressive. Boys with this form of the disease often pass away within a few years of beginning to show symptoms. [2] The other forms of X-ALD are less severe. The disease for these individuals may be slowly progressive, or it may not affect a person's lifespan at all. [2] It is important to remember that the exact signs and symptoms of a person with X-ALD cannot be predicted by the signs and symptoms of other members of the family. Therefore, the long-term outlook for individuals who have X-ALD within the same family can be very different. [2] Find a Specialist If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. If you can't find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care. You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists. Healthcare Resources To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference. 