Definition of Adrenoleukodystrophy:

X-linked adrenoleukodystrophy describes several closely related inherited disorders that disrupt the breakdown (metabolism) of certain fats (very-long-chain fatty acids).

Causes, incidence, and risk factors:

Adrenoleukodystrophy is passed down from parents to their children as an X-linked genetic trait. It therefore affects mostly males, although some women who are carriers can have milder forms of the disease. It affects approximately 1 in 20,000 people from all races.

The condition results in the buildup of very-long-chain fatty acids in the nervous system, adrenal gland, and testes, which disrupts normal activity. There are three major categories of disease:

• Childhood cerebral form -- appears in mid-childhood (at ages 4 - 8)
• Adrenomyelopathy --occurs in men in their 20s or later in life
• Impaired adrenal gland function (called Addison disease or Addison-like phenotype) -- adrenal gland does not produce enough steroid hormones

Symptoms:

Childhood cerebral type:

• Adrenal problems
• Changes in muscle tone, especially muscle spasms and spasticity
• Crossed eyes (strabismus)
• Decreased understanding of verbal communication (aphasia)
• Deterioration of handwriting
• Difficulty at school
• Difficulty understanding spoken material
• Hearing loss
• Hyperactivity
• Progressive nervous system deterioration
  • Coma
  • Decreased fine motor control
  • Paralysis
• Seizures
• Swallowing difficulties
• Visual impairment or blindness

Adrenomyelopathy:

• Adrenal problems
• Difficulty controlling urination
• Possible worsening muscle weakness or leg stiffness
• Problems with thinking speed and visual memory

Adrenal gland failure (Addison type):

• Coma
• Decreased appetite
• Increased skin pigmentation
• Loss of weight, muscle mass (wasting)
• Muscle weakness
• Vomiting

Signs and tests:

• Blood levels show elevated very-long-chain fatty acids
• Chromosome study shows ABCD1 gene mutations
• MRI of the head shows damage to the white matter of the brain (white matter is a type of brain tissue)

Treatment:

Adrenal dysfunction is treated with steroids (such as cortisol).

A specific treatment for X-linked adrenoleukodystrophy is not available, but eating a diet low in very-long-chain fatty acids and taking special oils can lower the blood levels of very-long-chain fatty acids.

These oils are called Lorenzo's oil, after the son of the family who discovered the treatment. This treatment is being tested for X-linked adrenoleukodystrophy, but it does not cure the disease and may not help all patients.

Bone marrow transplant is also being tested as an experimental treatment.

Expectations (prognosis):

The childhood form of X-linked adrenoleukodystrophy is a progressive disease that leads to a long-term coma (vegetative state) about 2 years after neurological symptoms develop. The child can live in this condition for as long as 10 years until death occurs.

The other forms of this disease are milder.

Complications:

• Adrenal crisis
• Vegetative state (long-term coma)

Calling your health care provider:

Call your health care provider if your child develops symptoms of X-linked adrenoleukodystrophy or if you have a child with X-linked adrenoleukodystrophy who is worsening.

Prevention:

Genetic counseling is recommended for prospective parents with a family history of X-linked adrenoleukodystrophy. The carrier state in females can be diagnosed in 85% of the cases using a very-long-chain fatty acid test and a DNA probe study by specialized laboratories.

Prenatal diagnosis of X-linked adrenoleukodystrophy is also available. It is done by evaluating cells from chorionic villus sampling or amniocentesis.