Fabry disease: detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype.
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.
Nakao
Shoichiro
S
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
Kodama
Chihaya
C
Takenaka
Toshihiro
T
Tanaka
Akihiro
A
Yasumoto
Yuichiro
Y
Yoshida
Aichi
A
Kanzaki
Tamotsu
T
Enriquez
Annette L D
AL
Eng
Christine M
CM
Tanaka
Hiromitsu
H
Tei
Chuwa
C
Desnick
Robert J
RJ
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
D000519:alpha-Galactosidase