title: No accumulation of globotriaosylceramide in the heart of a patient with the E66Q mutation in the α-galactosidase A gene.
abstract: BACKGROUND
  Fabry disease is an X-linked lysosomal disorder resulting from mutations in the α-galactosidase A (GLA) gene. Recent reports described that the E66Q mutation of GLA is not a disease-causing mutation. However, no pathological study was reported. We carried out pathological studies using a cardiac biopsy specimen from a patient with the E66Q mutation.
  
  
  METHODS
  The case was a 34 year old male patient with end-stage renal failure and cardiomegaly. He was diagnosed with gout at 15 years of age and hemodialysis was started for gouty nephropathy from 31 years of age. He was suspected of having Fabry disease as the result of a screening study for Fabry disease in patients with end-stage renal failure and was referred to our hospital for mutation analysis of the GLA gene. We carried out enzymatic and genetic analysis for GLA and pathological studies of a cardiac biopsy specimen.
  
  
  RESULTS
  The patient had the E66Q mutation in the GLA gene. GLA activity in leukocytes was 36.2% of the average of normal controls. The pathological study of the cardiac biopsy sample showed no characteristic findings of Fabry disease. The immunohistochemistry for GL3 of the cardiac biopsy sample showed no positive cells.
  
  
  CONCLUSIONS
  Although the E66Q mutation reduced enzyme activity, the characteristic pathological findings of Fabry disease and the abnormal accumulation of GL3 were not detected in cardiac tissues. The E66Q mutation of the GLA gene is thought to be a functional polymorphism based on enzymatic and pathological studies.
authors.affiliation: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan. masa-koba@jikei.ac.jp
authors.forename: Masahisa
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Yanagisawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inomata
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Teruo
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D004789:Enzyme Activation; D005091:Exons; D000795:Fabry Disease / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014281:Trihexosylceramides / Q000378:metabolism*; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase