Adrenoleukodystrophy Dr Trisha Macnair Adrenoleukodystrophy (ALD) is a rare inherited disorder that leads to progressive brain damage, failure of the adrenal gland and eventually death.

In this article

What is it? What causes it?

What are the symptoms? What's the treatment?

ALD is one of a group of inherited disorders called leukodystrophies in which the fatty covering of nerve fibres, the myelin sheath, is progressively damaged because of a faulty gene. Without the myelin sheath, the nerves don't work as they should.

People with adrenoleukodystrophy don't produce an essential protein, called a transporter protein. This is needed to carry an enzyme that breaks down very long chain saturated fatty acids (VLCFAs) taken into the body in the diet.

Accumulation of these VLCFAs in the brain and adrenal glands results in progressive deteriotation in brain and adrenal gland function.

There are several types of ALD, which may be inherited in two different ways.

ALD is most commonly inherited as an X-linked condition. This means the abnormal gene is found on the X chromosome.

Because women have two X chromosomes, they have a spare normal gene as well as the abnormal one, so generally only carry the condition. Men have only one X, so they are affected by the condition.

X-linked ALD may occur in three forms, with onset of symptoms in either childhood or adulthood.

Neonatal ALD is much less common. In this type of ALD the faulty gene isn't X-linked but is found on one of the other chromosomes. This means both boys and girls can be affected.

Symptoms develop as VLCFAs accumulate to very high levels in the brain and adrenal glands, causing damage to the nerves and other tissues.

Problems usually appear between the age of about four and ten

In childhood, X-linked ALD problems usually appear between the age of about four and ten.

Parents often notice changes in behaviour first. Next, memory and school performance begin to fall off and the child develops problems with vision, hearing, speech, swallowing, gait and coordination. There may be fatigue, seizures and sometimes an increase in skin pigmentation. Progressive dementia eventually leads to death.

Adult-onset X-linked ALD, also known as adrenomyeloneuropathy or AMN, usually begins between the ages of about 20 to 35.

Symptoms include stiffness, weakness or paralysis of the limbs and problems with muscle coordination (ataxia). With time, brain function deteriorates, although symptoms tend to progress more slowly than in the childhood form.

About one in five women carrying X-linked ALD develop a mild form of the condition in adulthood, with progressive symptoms similar to adult-onset ALD.

A third type of X-linked ALD leads to insufficiency of the adrenal gland at some point between two years and adulthood. At first there seems to be little neurological abnormality, but this may develop later.

In neonatal ALD, the newborn baby is usually floppy, with poor muscle tone and an abnormal facial appearance. The liver may be enlarged and seizures develop. There may also be degeneration of the retina and adrenal gland damage. Symptoms usually progress very rapidly.

There's no cure for ALD. Supportive treatments, including replacement of adrenal hormones, physiotherapy and special help at school, can control some of the symptoms or reduce their impact.

Research suggests that a mixture of oleic acid and euric acid, known as Lorenzo's oil, may delay or reduce symptoms in boys with X-linked ALD by lowering levels of VLCFAs. The most benefit is seen when the treatment is used before symptoms develop, before irreversible damage has occurred.

Bone marrow transplants have also been used with some success in boys in the early stages of X-linked ALD. Newer treatments that may lower brain levels of VLCFA are being tested.

Genetic research has identified the transporter proteins and their faulty genes, starting the path towards gene therapy.

This article was last medically reviewed by Dr Rob Hicks in October 2007