title: Isolated peripheral neuropathy in atypical metachromatic leukodystrophy: a recurrent mutation.
abstract: BACKGROUND
  Metachromatic leukodystrophy (MLD) is a genetic neurodegenerative disorder resulting from a deficiency of arylsulfatase A. Late onset forms are relatively rare. Central nervous system (CNS) involvement is characteristic at all ages.
  
  
  METHODS
  A patient in her late 40s with peripheral neuropathy was assessed by EEG, evoked potentials, CT and nerve conduction studies. Nerve and muscle biopsy samples were investigated by electron microscopy. Arylsulfatase A activity in leukocytes and excreted cerebroside sulfate were determined. The arylsulfatase A gene was investigated for mutations using polymerase chain reaction (PCR) and DNA sequencing. The identified mutation was expressed transiently in African green monkey kidney (COS) cells to determine the effect of the mutation on arylsulfatase A activity.
  
  
  RESULTS
  Central nervous system functions were normal. Nerve conduction velocities were decreased. Sural nerve biopsy showed inclusions typical of MLD. Arylsulfatase A was less than 5% of normal. A homozygous mutation thr286pro was identified in the arylsulfatase A gene and demonstrated to be deleterious through transient expression studies.
  
  
  CONCLUSIONS
  Our patient has a progressive peripheral neuropathy but has apparently intact CNS function at her present age of 57 years. Biochemical, physiological and pathological findings are consistent with a diagnosis of MLD. A homozygous mutation, thr286pro, found in her arylsulfatase A gene, decreased enzyme activity to a level consistent with a late onset form of MLD.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors.forename: Marion B
authors.initials: MB
authors.lastname: Coulter-Mackie
authors.forename: Derek A
authors.initials: DA
authors.lastname: Applegarth
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Toone
authors.forename: Liane
authors.initials: L
authors.lastname: Gagnier
authors.forename: André R
authors.initials: AR
authors.lastname: Anzarut
authors.forename: Glenda
authors.initials: G
authors.lastname: Hendson
mesh_terms: D000818:Animals; D001706:Biopsy; D019556:COS Cells; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000172:deficiency; D002554:Cerebrosides / Q000652:urine; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007194:India; D007962:Leukocytes / Q000378:metabolism; D007966:Leukodystrophy, Metachromatic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000648:ultrastructure; D020125:Mutation, Missense; D009431:Neural Conduction / Q000235:genetics / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013497:Sural Nerve / Q000648:ultrastructure
chemical_list: D002554:Cerebrosides; C083015:cerebroside sulfate; D002553:Cerebroside-Sulfatase