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Adrenoleukodystrophy: Rare Genetic Neurological and Endocrine Disease Affecting the Nervous System and Adrenal Glands

3 Forms: Childhood cerebral, Adrenomyeloneuropathy, Addison's Disease

Adrenoleukodystrophy is a rare genetic disease passed down from parent to child that affects the nervous system, adrenal glands, and/or testicles. The disease is more common, more severe and occurs earlier in males than females, and is found in approximately one in 20,000 people.


There are a variety of types of adrenoleukodystrophy that are grouped into 3 major categories:

  1. Childhood cerebral form (about 35% of all cases) —occurs in children, mostly four to eight years of ages, almost never seen before 3 years of age and rarely seen after age 15 years. It affects the brain and adrenal glands, and normally begins with severe learning and behavioral problems and if not caught early and treated, progresses over a few years to total disability and eventually death. Most affected children have defects in their adrenal glands, causing adrenal insufficiency, also called Addison’s disease (see below).
  2. Adrenomyeloneuropathy (about 40-45% of all cases)—a milder disease in adults with disease onset between 20-40 years of age and typically begins in the spinal cord, with symptoms, including weakness and stiffness in the legs. In approximately half of people with this disorder,  the disease affects the nerve cells in the brain. It also involves the adrenal glands and testicles in the majority of the patients.
  3. Addison’s disease only (about 10% of all cases)—occurs in adults and only the adrenal glands are affected. The glands can’t make enough steroid hormones (known as adrenal insufficiency) leading to weakness among other symptoms.
  • Note: 5-10% of patients may have atypical presentations (eg, headache and increased intracranial pressure in children, etc.).

Symptoms vary based on the type of the disease with the childhood cerebral form being the most severe and Addison’s disease being the mildest.

The disease is caused by a genetic defect of a gene (ABCD1 gene) on the X chromosome that causes a buildup of a specific type of fat in the body called very long-chain fatty acids. This buildup results in damage to the myelin sheath covering nerve cells in the brain and/or spinal cord, as well as to the adrenal gland and testicles, depending on what form of adrenoleukodystrophy a person has. The myelin sheath insulates and protects nerve cells and when it breaks down, the nerves have trouble transmitting messages to or from the brain, and the body loses control of certain functions.

The symptoms of adrenoleukodystrophy depend on the type of this disease:

Childhood cerebral form

  • Behavioral problems (withdrawal or aggression)
  • Memory problems and dementia
  • Learning disabilities
  • Hyperactivity
  • Speech/hearing problems
  • Eye problems, including vision loss and crossed eyes
  • Difficulty swallowing
  • Problems walking or with coordination
  • Seizures
  • Features of Addison’s disease (see below)


  • Weakness and stiffness in the legs that worsens over time
  • Difficulty walking or change in walking pattern
  • Trouble with muscle control
  • Problems urinating or loss of control of urination
  • Urinary and genital tract disorders
  • Behavioral changes
  • Vision changes
  • Features of Addison’s disease (see below)

Addison’s disease

  • Marked fatigue and weakness
  • Weight loss
  • Darkened skin (increased pigmentation)
  • Unexplained vomiting and decreased appetite
  • Lightheadedness and dizziness
  • Loss of consciousness, fainting

Early diagnosis of adrenoleukodystrophy is key to the potential success of treatment, especially with the childhood cerebral form. Diagnosis may be made using a simple blood test that measures the amount of very long-chain fatty acids in the blood. Magnetic resonance imaging of the brain, genetic testing to look for changes (mutations) in the ABCD1 gene, and skin biopsy also may be used.

  • To test for adrenal insufficiency, ACTH levels, and cortisol level at baseline and after ACTH stimulation are assessed.
  • Genetic counseling is recommended for people with a family history of adrenoleukodystrophy.
  • Diagnosis can be made using prenatal testing.

Treatment for adrenoleukodystrophy, due to its complexity and involvement of multiple organ systems, requires coordination of multiple specialties, including (but not all inclusive) neurology, endocrinology, and physical therapy.

Stem cell transplantation may slow or stop the progression of adrenoleukodystrophy in certain children if used early after diagnosis of the cerebral form of the disease. The stem cells used for transplantation are taken from donor bone marrow or donor umbilical cord stem cells. This transplant does carry risks and is normally not recommended in children with severe symptoms.

People with adrenal insufficiency will need replacement of adrenal steroids, including glucocorticoids (hydrocortisone, prednisone, dexamethasone, etc.) and mineralocorticoid (fludrocortisone). In addition, physical therapy and medications may help relieve some of the physical symptoms of adrenoleukodystrophy.

Use of Lorenzo’s oil, a mixture of oleic acid and erucic acid, is controversial. Some studies have shown that it may prevent or delay the childhood cerebral form from developing if given before children have symptoms, while other studies have not. A detailed discussion with your treating physician is needed to determine this treatment.

The childhood cerebral form is progressive (worsens over time) and may lead to a long-term coma a few years after symptoms develop if left untreated. The adult forms of this disease typically are milder, but may lead to early death in those who are severely affected or have adrenal crisis due to Addison’s disease.