International Encyclopedia of Rehabilitation


Association française contre l'adrénoleucodystrophie (AFCA)

Leukodystrophies refer to a group of genetically-determined progressive disorders characterized by degeneration of the white matter ('leuko') of the central nervous system (brain, spinal cord, or nerves), the most common form of which is adrenoleukodystrophy. Leukodystrophies are characterized by the great variability in the age of onset (from childhood to adulthood depending upon the specific type of leukodystrophy) and clinical signs. They most frequently lead to progressive neurological manifestations associated with impaired higher functions, and with severe and multiple disabilities.

What are leukodystrophies?

The term leukodystrophy has its origin in Greek leuko (white), trophy (growth) and dysfunction (disorder).. Thus, it describes a set of diseases that affect the growth or maintenance of the white matter or myelin, which is abundant in the nervous system. Myelin is also affected in multiple sclerosis. The prevalence rate of genetic leukodystophies is estimated to be 2 out of 10,000 in Europe. They mostly are neurolipidoses (lipid metabolism disorders) affecting the nervous system.

What are the clinical signs?

Onset: given the specific type of leucodystrophy, clinical signs may appear in the first month of life in the case of Canavan's disease (abnormal head size and blindness), while they may occur during adolescence, or even adulthood in the case of adrenomyeloneuropathy, Krabbe's sclerosis or metachromatic leukodystrophy (cf. table).

Progression: neurological manifestations are often progressive: changes are observed in muscle tone, gait, behavior, speech, sight, hearing, development of understanding, and memory. Without treatment, all of these manifestations can deteriorate rapidly (total paralysis, blindness, deafness, incontinence, inability to speak, and eat normally).

What are the causes?

The growth of myelin is ensured through the action of a series of essential proteins (enzymes), that are programmed and controlled by genes. Every genetic defect will therefore lead to an enzyme deficiency responsible for a structural change in the myelin.. This results in either a lack of an essential myelin component, or the excessive build-up of a given substance, which is toxic to the nerve cells. In any case, changes in the myelin sheath always lead to disturbances in function. Nervous signals can no longer be transmitted normally in the area where the myelin sheath is damaged.

The following table lists the types of leukodystrophies currently identified. Among these metabolic disorders, some some lysosomal storage diseases, (Krabbe's sclerosis, Refsum's disease, and metachromatic leukodystrophy). There is certain number of leukodystrophies (about 30%) for which the exact cause remains unknown.


Name (and myelin component affected) Inheritance Therapy (specific)
Metachromatic leukodystrophy (sulfatide) Autosomal recessive Bone marrow transplant
Krabbe's sclerosis (cerebroside) Autosomal recessive Bone marrow transplant
Adrenoleukodystrophy/adrenomyeloneuropathy (ALD-AMN) (long chain fatty acid) Sex link Diet and bone marrow transplant
Pelizaeus-Merzbacher disease (proteolipid) Sex link No
Alexander disease Unknown No
Neonatal adrenoleukodystrophy/Zellweger syndrome (very long chain fatty acid) Autosomal recessive No
Refsum's disease (phytanic acid) Autosomal recessive Special diet
Cerebrotendinous xanthomatosis (cholestanol) Autosomal recessive Chenodeoxycholic acid
Canavan's disease (N-acetylaspartic acid) Autosomal recessive No

Screening tests exist for some of the leukodystrophies and can be detected through blood or tissue samples (skin, muscles, intestinal membrane, liver). The characteristic changes associated with the disease can be detected easily. The diagnosis of leukodystrophies can be confirmed as early as during pregnancy.

What are the suggested treatments and managements strategies?

No radical, curative treatment is available, but specific treatments are possible in some cases. For example, cerebrotendinous xanthomatosis is treated though oral medication. For Refsum's disease, it is possible to downsize the phytanic acid level through a special diet (the muscle tone and peripheral nerve functions of patients are then restored to normal for these patients). Patients with ALD/AMN are placed on a low-fat diet to lower fatty acid levels in blood.

The bone marrow transplantation is another approach that has been experimented for some leukodystrophies: this amounts to the partial replacement of the missing enzyme to correct the deficiency. Given the risk of the transplantation itself, and the risk of further aggravation of the disease if it is done too late, it is considered only if compatible donors are available (preferably siblings) and when the disease it its early stage.

Three research approaches are used:

  • Gene isolation is the first step performed to identify the defective enzyme, the rectification of which can lead to a pharmacological solution;
  • Prevention of demyelination and facilitation of remyelination (Myelin Project);
  • Replacement of the defective gene (gene therapy) is the most promising hope against leukodystrophies in the long term.

For more information


ELA : Association Européenne contre les Leucodystrophies, 6 rue Pasteur, B.P. 267, 54005 Nancy Cedex.

AFCA : Association Française Contre l'Adrénoleucodystrophie, 11 hameau Saint-Jean, 13080 Luynes.


Association des paralysés de France. 1996. Déficiences motrices et handicaps, Aspects sociaux, psychologiques, médicaux, techniques et législatifs, troubles associés. Paris : Association des paralysés de France. 505 p. Used with permission.

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