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.
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.
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).
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