About Leukodystrophy

The word ‘leukodystrophy’ is the medical name given to a group of inherited, progressive genetic disorders caused by a defect in metabolism. The name comes from the Greek ‘leuko’, meaning white, and ‘dystrophy’, meaning imperfect growth or development.

How does leukodystrophy affect the nervous system?


The nerves in the human body are composed of two parts. The innermost section is called the axon and is directly responsible for conveying nerve impulses from the brain.

Surrounding the axon, rather like insulation around an electrical cord, is the myelin sheath, or ‘white matter‘. The sheath is made up of a variety of chemicals. Its protective covering is vital to the health and function of the nerve axon within.

In leukodystrophy, a mutation in one of the patient’s genes affects the development of one of the multiple chemicals (there are at least 10) that make up the myelin sheath, preventing or inhibiting its development.

Without this natural protection, the nerve axons are unable to function correctly. Each form of leukodystrophy affects a different element of the myelin sheath, causing a range of symptoms and affecting different parts of the nervous system, such as the spinal cord and the brain.

Leukodystrophy differs from other diseases of the myelin sheath, such as multiple sclerosis, because, rather than following an ‘up and down’ course, leukodystrophy is progressive – that is, the condition continues to get worse throughout the life of the sufferer.

There is a range of different leukodystrophies. While most leukodystrophies occur in children, some types affect adults.

How does leukodystrophy occur?

Leukodystrophy is a genetic, or inherited, disorder. Inheritance of a leukodystrophy can be either ‘autosomal recessive’ or ‘X-linked.’

Autosomal recessive disorders affect both boys and girls and require both parents to be carriers (heterozygotes). The carriers themselves have no disability. However, should two carriers have children together, on average there is a 25% chance of their child having the illness and a 50% chance of the child being a carrier.

The X-linked (sex-linked) disorders are carried on the X chromosome, with only the mother being the carrier. On average, half of the daughters of a woman who is a carrier will also be carriers, while the other half will not carry the gene. One-half of the woman’s sons will have the illness and the other half will not. If an affected man has children, then none of his sons will carry the disorder, but all of his daughters will be carriers.

There is no specific age for the onset of signs of leukodystrophy. A child who has been fit and well may gradually show signs of a loss of hearing and/or vision, as well as changes in body tone, movement, gait, balance, speech, ability to eat, behaviour, memory or thought processes. There are also people who carry a leukodystrophy gene who are healthy as children or young adults, but develop leukodystrophy later in adult life.

As leukodystrophies are genetically determined, they are not contagious.

Many other disorders may show similar signs and symptoms, and a doctor is unlikely to consider leukodystrophy until the possibility of more common diseases has been ruled out.

Management of leukodystrophy

The leukodystrophies are almost invariably incurable. However, support from physicians, nurses, physiotherapists, occupational therapists, nutritionists, educators, psychologists and other parents can assist. This support can include family counselling, respite care, and advice on matters such as medications and social security entitlements.

Active research into the leukodystrophies is happening worldwide. New and experimental therapies are constantly being tested and tried to overcome the effects of the various causes of leukodystrophy and to either reduce the symptoms, slow the progression, or halt the progress of the disease altogether.

Some of the leukodystrophies respond to relatively simple therapies. For example, cerebrotendinous xanthomatosis patients can be helped by taking a simple oral medication.

The fat which accumulates in the blood of patients with Refsum’s disease (phytanic acid), for example, can be cleared by the implementation of a diet which restricts the intake of this fat in the diet. This can be beneficial for muscle strength and nerve function, and can arrest the deterioration of vision and hearing.

International clinical trials on the effects of Lorenzo’s Oil therapy on adrenoleukodystrophy are in progress. The studies mostly involve patients who carry the abnormal gene but have not yet developed the disease. It has already been established that this treatment can reduce the levels of the very long chain fats in the blood (these substances accumulate in the tissues and blood of patients and are believed to contribute to the disease), but as yet it is not known whether damage to the brain can be prevented.

Another form of therapy which is showing promise is the partial replacement of the inactive protein with active protein. This can be achieved by bone marrow transplantation. Cells derived from the transplant, which contain normal active protein, are able to handle the substance which the patient’s body is unable to cope with. This form of therapy has already been used to treat some of the leukodystrophies, such as ALD and MLD.

However, matched donors must be available, the procedure carries a risk, and there is still a question as to the extent to which the bone marrow cells can enter the brain – the organ most affected by leukodystrophy. Also, it is preferable that the procedure be used before possible irreversible damage to the brain occurs.

An alternative approach is enzyme replacement therapy, in which the patient is administered the active protein obtained from some other source. Perhaps the most exciting development is the replacement of the gene itself. In March 1996, in New Zealand, the world’s first human gene therapy trials for a neurological disease were carried out on two children with Canavan disease. Further trials involving more children were conducted in early 1998.

Research is ongoing, and every year further progress is made.