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