title: Fabry disease: detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype.
abstract: BACKGROUND
  Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient alpha-galactosidase A (alpha-Gal A) activity. Renal failure is a major debilitating complication in classically affected males. To determine if this disorder is underdiagnosed in patients with end-stage renal disease (ESRD), the frequency of unrecognized males with Fabry disease on chronic hemodialysis was determined.
  
  
  METHODS
  Plasma alpha-Gal A activity was measured in 514 consecutive males with ESRD on hemodialysis. Patients with low alpha-Gal A activity were evaluated clinically and their alpha-Gal A mutations were determined.
  
  
  RESULTS
  Six (1.2%) of 514 hemodialysis patients had low plasma alpha-Gal A activities and a previously identified (E66Q, A97V, M296I) or novel (G373D) missense mutation. At ages 30 to 68 years, five patients lacked the classic manifestations of angiokeratoma, acroparesthesias, hypohidrosis, and ocular opacities, while the sixth lacked angiokeratoma and ocular changes. Five had left ventricular hypertrophy (LVH).
  
  
  CONCLUSIONS
  The clinical spectrum of Fabry disease includes a "renal variant" phenotype in patients without classic symptoms who develop ESRD. Affected males undergoing hemodialysis or renal transplantation can be readily diagnosed by plasma alpha-Gal A assays. These patients and their family members may benefit from enzyme replacement therapy for the later, life-threatening cardiovascular and cerebrovascular complications of Fabry disease.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Nakao
authors.forename: Chihaya
authors.initials: C
authors.lastname: Kodama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takenaka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yasumoto
authors.forename: Aichi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanzaki
authors.forename: Annette L D
authors.initials: AL
authors.lastname: Enriquez
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Chuwa
authors.initials: C
authors.lastname: Tei
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000628:therapy*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D006435:Renal Dialysis; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics
chemical_list: D000519:alpha-Galactosidase