Metachromatic leukodystrophy is an autosomal recessive disease that affects both children and adults.
Summary
Cause
Metachromatic leukodystrophy (OMIM #250100) is caused by mutations in the ARSA gene, which codes for arylsulfatase A (ARSA), and in rare cases, by mutations in the PSAP gene, which codes for saposin-B (necessary for ARSA activity). It is a lysosomal storage disease within the metabolic leukodystrophies, with an estimated incidence between 1/40,000 and 1/170,000.
ARSA deficiency leads to the accumulation of sulfatides (major sphingolipids that make up 30% of the lipid content of myelin) within lysosomes, primarily in the central and peripheral nervous systems, causing demyelination and subsequent neuronal degeneration.
Symptoms
The first symptoms of metachromatic leukodystrophy can appear in childhood or adulthood. In the most severe forms, the disease can be devastating, leading to rapid motor and cognitive decline and premature death.
Metachromatic leukodystrophy is classified into infantile, juvenile, and adult forms. The natural progression of the adult form, which is rare and highly variable, is not well described. Patients usually experience cognitive and/or psychiatric symptoms, followed by motor deterioration, sometimes years later.
There is a relative correlation between phenotype, genotype, and residual enzyme activity.
Treatment
In adults, hematopoietic stem cell transplantation, preferably using bone marrow, is an option for presymptomatic or very early symptomatic patients.