Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a “renal variant” phenotype1

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 α-galactosidase A (α-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 α-Gal A activity was measured in 514 consecutive males with ESRD on hemodialysis. Patients with low α-Gal A activity were evaluated clinically and their α-Gal A mutations were determined. Results Six (1.2%) of 514 hemodialysis patients had low plasma α-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). Conclusion 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 α-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.