Metachromatic leukodystrophy

Metachromatic leukodystrophy is an inherited lysosomal storage disease, usually caused by arylsulfatase A deficiency. Sulfatides accumulate and progressively damage myelin in the nervous system.

Arylsulfatase A: A lysosomal enzyme that breaks down sulfatides and other sulfated lipids. Its deficiency is the most common cause of sulfatide accumulation in this disease.
Autosomal recessive inheritance: A pattern in which disease usually occurs when a person inherits pathogenic variants in both copies of a gene. Most cases arise when both inherited copies of ARSA or PSAP are affected.
Newborn screening: Testing newborns for selected conditions before symptoms appear, allowing early diagnosis and intervention. Screening programs can identify affected infants before neurological decline becomes apparent.
Juvenile metachromatic leukodystrophy: A form of metachromatic leukodystrophy with symptom onset during childhood or adolescence. Its slower onset and early behavioral or school difficulties contrast with the infantile form.
Sulfatide: A sulfated glycosphingolipid abundant in myelin and certain other tissues. This lipid accumulates when its lysosomal degradation is impaired.
ARSA: A gene that encodes the lysosomal enzyme arylsulfatase A. Pathogenic variants in this gene account for most cases of metachromatic leukodystrophy.
Genetic testing: Analysis of DNA to identify variants associated with a condition or trait. Testing ARSA and PSAP can confirm the molecular cause and support family counseling.
Adult metachromatic leukodystrophy: A form of metachromatic leukodystrophy whose symptoms begin in adulthood. Psychiatric or cognitive changes may precede prominent motor symptoms in this form.
Lysosome: A membrane-bound cell organelle that degrades macromolecules using acidic enzymes. Defective lysosomal degradation lies at the start of the disease pathway.
PSAP: A gene encoding prosaposin, the precursor of several lysosomal activator proteins. Variants affecting its saposin B component can produce the disease phenotype.

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