ALD Disease

What is ALD Disease

ALD Disease is one of a group of disorders called the leukodystrophies where the fatty covering of nerve fibres, called the myelin sheath, breaks down. There's no cure, although intensive research is being carried out for effective treatments.

Parents watch with growing anxiety as their child becomes abnormally withdrawn or aggressive

It's a devastating disease, not least because in its most severe form it starts to make its mark just as an apparently healthy young boy is beginning to leap and bound towards adult life. Parents watch with growing anxiety as their child becomes abnormally withdrawn or aggressive. A steady deterioration in brain function may then occur as the disease follows a relentless course towards death, which usually occurs within ten years of onset of symptoms and often much sooner.

What causes ALD Disease?

ALD Disease is one of several inherited disorders where the myelin sheath - the fatty insulating layer that covers many of the neurons - is progressively damaged, because of a faulty gene. Without the myelin sheath the nerves don't work as they should.There are several different types of ALD Disease, which may be inherited in two different ways.

ALD Disease 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 they generally only carry ALD Disease. But men have only the one faulty X, so they are affected by the condition. X-linked ALD Disease may occur in three forms, with onset of symptoms in either childhood or in adulthood.

Neonatal ALD Disease is much less common. In this type of ALD Disease the faulty gene is not X-linked but found on one of the other chromosomes, so both boys and girls can be affected.

Symptoms of ALD Disease

People with ALD Disease don't produce an essential protein, called a transporter protein. This protein is needed to carry an enzyme that breaks down very long chain saturated fatty acids (VLCFAs) taken into the body in the diet. If these VLCFAs aren't broken down they may accumulate to very high levels in the brain and in the adrenal cortex, causing damage to the nerves and other tissues.

There may be fatigue, seizures and sometimes an increase in skin pigmentation

As VLCFAs build up, so symptoms develop. In childhood, X-linked ALD Disease problems usually appear between the age of about four and ten. Parents often notice changes in behaviour first. Then 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.

The adult-onset form of X-linked ALD Disease, 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, called 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 Disease develop a mild form in adulthood, with progressive symptoms similar to adult-onset ALD Disease.

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

In neonatal ALD Disease, 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.

Treatment of ALD Disease

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

'Lorenzo's oil' may delay or reduce symptoms in boys with X-linked ALD Disease

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 Disease, by lowering levels of VLCFAs. The oil takes its name from the film about Lorenzo Odone, a boy who suffers with ALD Disease. The most benefit is seen when the treatment is used before symptoms develop, before irreversible damage has occurred. However, other experts say that Lorenzo's survival is more simply a reflection of variability of the disease and the intense efforts of his parents to look after him.

Bone marrow transplants have also been used with some success in boys with the early stages of X-linked ALD Disease. Newer treatments that may lower brain levels of VLCFA are being tested. Meanwhile genetic research has identified the transporter proteins and their faulty genes, starting the path towards gene therapy.