Metachromatic leukodystrophy is also known as or subsumes Arylsulfatase A pseudodeficiency, Metachromatic leukodystrophy, Multiple sulfatase deficiency, Sulfatide activator deficiency, and Sulfatase modifier factor 1. -ed.
Metachromatic leukodystrophy is an autosomal recessive disorder caused by mutations in the arylsulfatase A (ARSA) gene. The severity of the clinical syndrome varies from infantile regression, hypotonia, peripheral neuropathy, seizures, and cognitive deterioration to late adult-onset behavioral disturbance, often initially diagnosed as a primary psychiatric disorder followed by spastic paraparesis, seizures, and dementia. The syndrome severity is primarily determined by the level of residual enzymatic activity. Guidelines are presented to differentiate metachromatic leukodystrophy from the related syndromes of multiple sulfatase deficiency, and of sulfatide activator deficiency and from the “pseudodeficiency” state. In this update, Dr. Alessandra Biffi and Dr. Maria Sessa of the San Raffaele Scientific Institute in Milan, Italy, and Dr. James Garbern of the University of Rochester School of Medicine and Dentistry report on the more recent advances in genotype-phenotype correlation and on the status of therapy of metachromatic leukodystrophy by bone marrow transplantation, stem cell therapy, and gene therapy.