Metachromatic leukodystrophy panel [3 genes]

Metachromatic leukodystrophy is an autosomal recessive metabolic hereditary disease characterized by the accumulation of sulfatides in various tissues, which produces progressive demyelination in the central and peripheral nervous systems and progressive decline in motor and cognitive functions.

In most cases, this disease is caused by a deficiency of the arylsulfatase A enzyme, encoded by the ARSA gene, giving rise to the accumulation of 3′-O-sulfogalactosylceramide (sulfatide) in oligodendrocytes, Schwann cells, and some neurons. Also, some pathogenic variants resulting in saposin B deficiency have been identified in the gene that encodes prosaposin (PSAP), which is involved in the lysosomal hydrolisis of sphingolipids. Finally, homozygous pathogenic variants in the SUMF1 gene (which encodes an enzyme necessary for post-translational modification and catalytic activation of sulfatases) give rise to multiple sulfatase deficiency, which is characterized by the accumulation of sulfates, sulfated glycosaminoglycans, sphingolipids and steroid sulfates, and which combines the characteristics of metachromatic leukodystrophy and various mucopolysaccharidoses.