In Metachromatic leukodystrophy, which also called Arylsulfatase A deficiency, is a rare genetic disorder and a part of a larger group of lysosomal storage diseases. More precisely, it affects the growth and/or development of myelin that acts as an insulator around nerve fibers throughout the central and peripheral nervous systems. This deficiency of the enzyme that helps break down fatty substances causes the lipids to build up in the brain, spinal cord and peripheral nerves. As a result of that, the brain and the nervous system progressively lose function. Rarely, this condition is caused by a deficient non-enzyme protein (that is called ‘activator protein’).
Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which may overlap. Those are:
- Infantile form, occurring between ages 6 months and 2 years. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Untreated, most children with this form of MLD die by age 5, often much sooner.
- Juvenile form, occurring between ages 3 and 6 (early juvenile) or between ages 6 and 16 (late juvenile). Children usually begin with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the late infantile form but with slower progression.
- Adult form, occurring at age 17 or older. This form commonly begins after age 16 as a psychiatric disorder or progressive dementia. Adult-onset MLD progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.
MLD is directly caused by a deficiency of the enzyme Arylsulfatase A (ARSA) and is characterized by enzyme activity in leukocytes that is less than 10% of normal controls. However, assay of the ARSA enzyme activity alone is not sufficient for diagnosis; ARSA pseudo-deficiency, which is characterized by enzyme activity that is about 20% of normal controls does not cause MLD. Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.