title: Metachromatic leukodystrophy: Disease spectrum and approaches for treatment.
abstract: Metachromatic leukodystrophy is an inherited lysosomal disorder caused by recessive mutations in ARSA encoding arylsulfatase A. Low activity of arylsulfatase A results in the accumulation of sulfatides in the central and peripheral nervous system leading to demyelination. The disease is classified in a late-infantile, juvenile and adult onset type based on the age of onset, all characterized by a variety of neurological symptoms, which eventually lead to death if untreated. There is no curative treatment for all types and stages. This review discusses diagnostic process and efficacy of current and possible future therapies such as hematopoietic stem cell transplantation, enzyme replacement therapy and gene therapy. A systematic evaluation regarding the efficacy of hematopoietic stem cell transplantation and a longer follow up period for gene therapy are needed to come to a general conclusion and improve treatment options for metachromatic leukodystrophy.
authors.affiliation: Department of Child Neurology, Center for Children with White Matter Disorders, VU Medical Centre and Neuroscience Campus, Postbox 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: d.vanrappard@vumc.nl.
authors.forename: Diane F
authors.initials: DF
authors.lastname: van Rappard
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplantation Program, University Medical Center Utrecht, PO Box 85090, 3503 AB Utrecht, The Netherlands. Electronic address: j.j.boelens@umcutrecht.nl.
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Boelens
authors.affiliation: Department of Child Neurology, Center for Children with White Matter Disorders, VU Medical Centre and Neuroscience Campus, Postbox 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: n.wolf@vumc.nl.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
mesh_terms: D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000150:complications* / Q000473:pathology / Q000628:therapy; D008279:Magnetic Resonance Imaging; D010523:Peripheral Nervous System Diseases / Q000209:etiology*
keywords: enzyme replacement therapy; gene therapy; hematopoietic stem cell transplantation; leukodystrophy; magnetic resonance imaging; metachromatic