Leukodystrophy is a neurodegenerative disease caused by a build-up of sulfatides (a type of glycolipid) in the brain.

Leukodystrophy is a neurodegenerative pathology. It is the consequence of an abnormal accumulation in the nervous system of a substance which combines lipid and carbohydrate: a glycolipid. These glycolipids, the source of leukodystrophy, are sulfatides. the disease is therefore the consequence of an accumulation of sulfatides in the nervous system, but also in the kidneys.

Leukodystrophy is a rare disease, with an incidence of between 0.5 and 1 case in 50 individuals.

Three forms of leukodystrophy

• the late infantile form: for nearly 60% of leukodystrophy cases
• the juvenile form: which concerns between 20% and 30% of cases of leukodystrophy
• the adult form: which concerns between 10% and 20% of cases of leukodystrophy

The late infantile form is therefore the most frequent. This first form appears from the first steps of the child. The latter then presents with hypotonia (weakening of muscle tone), disturbances in the way he walks, optic atrophy (inflammation of the optic nerve), or even regression of motor skills.

Leukodystrophy is an inherited genetic disease. It is inherited in an autosomal recessive fashion. That is to say that the mutated gene of interest is located on an autosome (non-sexual chromosome) and that the presence of two copies of the gene in question is necessary in the development of the disease (one from the mother, and one from the father).

The presence of the mutated gene causes an abnormality in the formation of the enzyme capable of degrading sulfatides in the brain. Depending on the forms of the disease, this inability to remove these substances from the brain is more or less important. Indeed, in the infantile form, the enzymatic activity is almost zero. In the juvenile form, this deficiency in enzyme activity is less important. Finally, in the context of an adult form, the enzymatic activity remains residual.

As this is an autosomal recessive inherited disease, patients with leukodystrophy therefore have their father and mother also suffering from the disease.

The recessive nature of leukodystrophy means that if the child has only one copy of the gene of interest, it will not present the characteristics of the disease. The presence of two copies of the mutated gene is necessary in the development of the pathology.

The build-up of sulfatides in the brain causes decerebration (destruction of the brain). This usually occurs 5 years after the first clinical signs.

Therefore, the search for these substances in the urine or sulfatiduria is important and essential in the early and rapid management of the disease.

Leukodystrophy is a neurodegenerative disease. The clinical signs and associated symptoms relate to:

• motor disorders (walking for example)
• psychiatric manifestations (behavioral disorders, chronic anxiety, etc.)
• epileptic seizures
• optic atrophy

Leukodystrophy being a recessive hereditary genetic disease, the only risk factor is therefore the presence of the mutated gene in the family context (presence in the father and in the mother).

Currently, no cure for the disease has yet been developed. A therapy based on the substitution of the deficient enzyme is under study.

In the context of childhood or juvenile leukodystrophy, a bone marrow transplant stabilizes neurocognitive functions but this is not completely guaranteed.