Identification of Fabry's disease by the screening of alpha-galactosidase A activity in male and female hemodialysis patients.
BACKGROUND
Although previous studies reported that the prevalence of Fabry's disease was 0.16 - 1.2% in hemodialysis (HD) patients based on measurement of a-galactosidase A (alpha-Gal A) activity, few reports detected female patients by the screening for alpha-Gal A. Here we determined the prevalence of Fabry's disease not only in male but also in female HD patients by measuring alpha-Gal A.


METHODS
Plasma alpha-Gal A was measured in 696 consecutive males (n = 401) and females (n = 295) on HD. Patients with low plasma alpha-Gal A were examined for leukocyte alpha-Gal A, and patients with low leukocyte alpha-Gal A underwent alpha-Gal A gene sequence analysis for possible mutations, and family survey.


RESULTS
Among 15 patients with low plasma alpha-Gal A activity, 4 male patients with low leukocyte alpha-Gal A and 1 female patient revealing low plasma alpha-Gal A were detected in 696 HD patients (0.7% of total patients). 3 of these 5 patients were already diagnosed to have the classical type of Fabry's disease. The other 2 patients were newly diagnosed as Fabry's disease, and did not have typical manifestations of Fabry's disease other than renal failure and left ventricular hypertrophy. DNA analysis of these 2 newly diagnosed patients revealed that each had an alpha-Gal missense mutation, previously identified (E66Q, M2961).


CONCLUSIONS
Fabry's disease should be considered in the etiology of unexplained end-stage renal disease. Not only affected males but also affected females undergoing HD patients can be readily diagnosed by alpha-Gal A activities and gene analysis. These patients and their family members may benefit from enzyme replacement therapy for Fabry's disease.
Tanaka
M
M
Department of Nephrology, Akebono Clinic, 5-1-1 Shirafuji, Kumamoto 861-4112, Japan. tanaka@matusita-kai.or.jp
Ohashi
T
T
Kobayashi
M
M
Eto
Y
Y
Miyamura
N
N
Nishida
K
K
Araki
E
E
Itoh
K
K
Matsushita
K
K
Hara
M
M
Kuwahara
K
K
Nakano
T
T
Yasumoto
N
N
Nonoguchi
H
H
Tomita
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000032:analysis; D018450:Disease Progression; D005091:Exons; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D006435:Renal Dialysis; D012720:Severity of Illness Index; D000519:alpha-Galactosidase / Q000097:blood* / Q000235:genetics
D015415:Biomarkers; D004247:DNA; D000519:alpha-Galactosidase