title: X-linked adrenoleukodystrophy: pathogenesis and treatment.
abstract: X-linked adrenoleukodystrophy (X-ALD) is a puzzling inborn error of metabolism with a strikingly heterogeneous clinical spectrum. All patients have mutations in the ABCD1 gene and accumulate very long chain fatty acids in all tissues. Virtually all male X-ALD patients develop adrenocortical insufficiency in childhood and progressive myelopathy and peripheral neuropathy in adulthood. A subset of male patients, however, develops a fatal cerebral demyelinating disease, cerebral adrenoleukodystrophy. Female patients also develop progressive myelopathy and peripheral neuropathy, but generally at a later age than males. They only very rarely develop adrenocortical insufficiency or cerebral adrenoleukodystrophy. This review proposes to simplify the classification of the clinical spectrum of X-ALD and reviews the largely unresolved pathophysiological mechanisms and the current treatment options.
authors.affiliation: Department of Pediatric Neurology/Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, 1100 DD, The Netherlands, m.engelen@amc.uva.nl.
authors.forename: Marc
authors.initials: M
authors.lastname: Engelen
authors.forename: Stephan
authors.initials: S
authors.lastname: Kemp
authors.forename: Bwee-Tien
authors.initials: BT
authors.lastname: Poll-The
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000224:Addison Disease / Q000209:etiology; D000326:Adrenoleukodystrophy / Q000150:complications* / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D018450:Disease Progression; D006801:Humans; D009154:Mutation / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D013118:Spinal Cord Diseases / Q000209:etiology
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters