Adrenoleukodystrophy

Definition

Adrenoleukodystrophy is a rare genetic disease characterized by a loss of myelin surrounding nerve cells in the brain and progressive adrenal gland dysfunction.

Description

Adrenoleukodystrophy (ALD) is a member of a group of diseases, leukodystrophies, that cause damage to the myelin sheath of nerve cells. Approximately one in 100,000 people is affected by ALD.


There are three basic forms of ALD: childhood, adult-onset, and neonatal. The childhood form of the disease is the classical form and is the most severe. Childhood ALD is progressive and usually leads to total disability or death. It affects only boys because the genetic defect is sex-linked (carried on the X chromosome). Onset usually occurs between ages four and ten and can include many different symptoms, not all of which appear together. The most common symptoms are behavioral problems and poor memory. Other symptoms frequently seen are loss of vision, seizures, poorly articulated speech, difficulty swallowing, deafness, problems with gait and coordination, fatigue, increased skin pigmentation, and progressive dementia.

The adult-onset form of the disease, also called adrenomyeloneuropathy, is milder, progresses slowly, is usually associated with a normal life span, and usually appears between ages 21-35. Symptoms may include progressive stiffness, weakness, or paralysis of the lower limbs and loss of coordination. Brain function deterioration may also been seen. Women who are carriers of the disease occasionally experience the same symptoms, as well as others, including ataxia, hypertonia (excessive muscle tone), mild peripheral neuropathy, and urinary problems. The neonatal form affects both male and female infants and may produce mental retardation, facial abnormalities, seizures, retinal degeneration, poor muscle tone, enlarged liver, and adrenal dysfunction. Neonatal ALD usually progresses rapidly.



Causes and symptoms

The genetic defect in ALD causes a decrease in the ability to degrade very long chain fatty acids. These build up in the adrenal glands, brain, plasma, and fibroblasts. The build-up of very long chain fatty acids interferes with the ability of the adrenal gland to convert cholesterol into steroids and causes demyelination of nerves in the white matter of the brain. Demyelinated nerve cells are unable to function properly.

Diagnosis

Diagnosis is made based on observed symptoms, a biochemical test, and a family history. The biochemical test detects elevated levels of very long chain fatty acids in samples from amniocentesis, chorionic villi, plasma, red blood cells, or fibroblasts. A family history may indicate the likelihood of ALD because the disease is carried on the X-chromosome by the female lineage of families.

Treatment

Treatment for all forms of ALD consists of treating the symptoms and supporting the patient with physical therapy, psychological counseling, and special education in some cases. There is no cure for this disease, and there are no drugs that can reverse demyelination of nerve and brain cells. Dietary measures consist of reducing the intake of foods high in fat, which are a source of very long chain fatty acids. A mixture called Lorenzo's Oil has been shown to reduce the level of long chain fatty acids if used long term; however, the rate of myelin loss is unaffected. Experimental bone marrow transplantation has not been very effective.

Prognosis

Prognosis for childhood and neonatal ALD patients is poor because of the progressive myelin degeneration. Death usually occurs between one and ten years after onset of symptoms.

Prevention

Since ALD is a genetic disease, prevention is largely limited to genetic counseling and fetal monitoring through amniocentesis or chorionic villus sampling.