Metachromatic leukodystrophy is a neurodegenerative disease characterized by accumulation of sulfatide (sulfated glycosphingolipid, especially sulfoglucuronylcerebroside or sulfogalactosilceramidas) in the central nervous system and kidney.
There are three forms of the disease: late infantile, juvenile and adult. Its incidence varies between 0.5 and 1/50,000 (with 60% late childhood, 20-30% juvenile and 10-20% adult). The estimated prevalence is 1 in every 625,000.
The late infantile form is the most common and usually starts at the same age you learn to walk, hypotonia, walking difficulties, optic atrophy and motor regression preceding mental impairment. The peripheral nervous system is systematically affected (decreased nerve conduction velocities occurs). The disorder progresses to a state of decerebration after a few years, resulting in death within 5 years after the onset of symptoms. Symptoms of sulfatide accumulation should be monitored systematically, especially in urine.
The juvenile form begins around 4 or 5 years old, with detention of intellectual development, followed by motor regression, epileptic seizures and ataxia. The disease does not progress as quickly as the child, but the result ends up being equally fatal, most patients die before reaching 20 years of age.
In the adult form, the onset occurs around age 15, although often no diagnosis until adulthood. Clinical signs include both motor disorders such as psychiatric, albeit with a slower progression. The disease can manifest as epileptic seizures. The sulfatiduria is always present but to a lesser degree than in earlier onset forms.
Metachromatic leukodystrophy is inherited in an autosomal recessive manner and is the result of an inability to metabolize cerebroside sulfate. In most cases, the enzyme deficiency is arylsulfatase A. In the late infantile form, the activity of arylsulfatase A is from very low to non-existent. In the juvenile form, enzyme deficiency and sulfatiduria are also present but in a way.
There is no specific treatment available for this disorder. Bone marrow transplantation may be useful in patients with late infantile form or juvenile if applied before the onset of symptoms, in order to stabilize their neurocognitive functions although its effectiveness is not guaranteed. It is currently investigating the use of a replacement enzyme therapy.
Gene or region studied