Adrenoleukodystrophy (ALD) is a rare inherited genetic disorder that primarily affects the brain, spinal cord, and adrenal glands. It damages the myelin, the protective covering that surrounds nerve cells and allows them to transmit signals properly. As myelin breaks down, nerve function can progressively deteriorate. ALD is caused by changes (mutations) in the ABCD1 gene. The condition primarily affects males, although females who carry the altered gene may also develop symptoms, usually in a milder form. There are several forms of ALD. The most severe form in children, childhood cerebral ALD, can cause progressive problems with learning, behavior, movement, vision, hearing, and other neurological functions. Other forms may primarily affect the adrenal glands or the spinal cord and peripheral nerves.
Symptoms vary depending on the type of ALD and the age at which it develops. They may include:
Muscle weakness
Muscle spasms or stiffness
Seizures
Difficulty swallowing
Slurred speech
Hearing impairment or hearing loss
Impaired vision, which may progress to blindness
Difficulty walking or problems with coordination
Changes in behavior or personality
Hyperactivity or difficulty concentrating
Problems with memory, learning, or school performance
Loss of appetite
Unexplained weight loss
Nausea and vomiting
Progressive paralysis
Loss of bladder or bowel control
Severe neurological impairment
Coma in advanced cases
Some people with ALD develop adrenal insufficiency (Addison’s disease). This can cause fatigue, weakness, weight loss, low blood pressure, abdominal symptoms, low blood sugar, and darkening of the skin.
ALD is caused by a mutation in the ABCD1 gene, which is located on the X chromosome. This gene provides instructions for making a protein involved in transporting certain fatty acids into peroxisomes, structures within cells that help break down fatty acids. When the ABCD1 gene does not function properly, very-long-chain fatty acids (VLCFAs) can accumulate, particularly in the nervous system and adrenal glands. Their buildup is associated with damage to myelin and adrenal tissue. Because ALD is X-linked, males are generally more severely affected because they have one X chromosome. Females have two X chromosomes and may have a milder form of the disease, although some women can develop significant neurological symptoms.
This form usually begins during childhood and can progress rapidly. Early symptoms may include difficulty learning, behavioral changes, declining school performance, vision or hearing problems, and problems with coordination. Without appropriate treatment, severe neurological disability can develop.
AMN is a form that generally begins in adulthood. It mainly affects the spinal cord and peripheral nerves and may cause progressive stiffness and weakness of the legs, difficulty walking, balance problems, and bladder or bowel difficulties.
Some people with ALD primarily develop adrenal gland dysfunction. The adrenal glands produce hormones that are important for maintaining blood pressure, blood sugar, metabolism, and the body’s response to stress. Adrenal insufficiency can occur before neurological symptoms and requires prompt medical management.
The major risk factor for ALD is having an ABCD1 gene mutation. A family history of ALD can increase the likelihood of inheriting the condition. Genetic counseling and testing may be recommended for affected families because the disorder can be passed from one generation to another.
Hematopoietic stem cell transplantation (HSCT) may be considered for certain boys with early-stage childhood cerebral ALD, particularly when brain MRI shows evidence of disease but neurological impairment is still limited. Treatment is generally most beneficial when performed before substantial neurological deterioration. HSCT carries significant risks and is not appropriate for every person with ALD. The decision requires assessment by a specialized medical team.
People who develop adrenal insufficiency may require lifelong hormone replacement therapy, usually with glucocorticoids and, in some cases, mineralocorticoids. Regular monitoring is important because an untreated adrenal crisis can be life-threatening.
A child with unexplained changes in learning, behavior, vision, hearing, coordination, or movement should be evaluated by a healthcare professional, particularly when there is a family history of ALD. Urgent medical attention is required for symptoms that may indicate adrenal crisis, such as severe weakness, vomiting, abdominal pain, confusion, fainting, very low blood pressure, or loss of consciousness.
ALD is a lifelong condition that requires ongoing medical monitoring. Regular neurological assessments, adrenal function testing, and appropriate imaging can help doctors identify disease progression and complications. Families may benefit from genetic counseling to understand inheritance patterns, testing options, and the potential risk to other family members. Early identification of affected children can be particularly important because some treatments are time-sensitive.
Yes. Boys are generally more severely affected because they have only one X chromosome. Women who carry an ABCD1 mutation can also develop symptoms, particularly later in life, although these are often less severe.
There is currently no treatment that cures all forms of ALD. However, selected children with early cerebral ALD may benefit from hematopoietic stem cell transplantation, while adrenal insufficiency can be treated with hormone replacement.
Yes. Adrenal insufficiency caused by ALD can usually be managed with appropriate hormone replacement therapy. Patients require ongoing monitoring and may need increased steroid doses during illness, injury, or other physical stress.
No. ALD has a variable course. Some people develop childhood cerebral disease, while others primarily develop adrenal insufficiency or adult-onset neurological symptoms.
Medical Disclaimer: This article is intended for general educational purposes and should not be considered a substitute for professional medical advice, diagnosis, or treatment. Anyone with symptoms suggestive of ALD or a family history of the condition should consult a qualified healthcare professional.
