Screening for Fabry disease in patients with chronic kidney disease: limitations of plasma alpha-galactosidase assay as a screening test.

BACKGROUND AND OBJECTIVES Fabry disease is a progressive X-linked disorder of glycosphingolipid metabolism that typically presents in childhood and progresses to heart failure and renal failure in adulthood. This study sought to determine the prevalence of Fabry disease in a multiethnic male chronic kidney disease population, involving dialysis-dependent, non-dialysis-dependent, and transplant patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 499 patients were screened with assay of alpha-galactosidase activity using fluorometric enzyme assay on plasma prepared from fresh heparinized blood, followed by leukocyte alpha-galactosidase activity in the subset of patients with plasma alpha-galactosidase activity below the second percentile (corresponding to a value <3.0 nmol/h per ml plasma). RESULTS This study did not identify any new cases of Fabry disease; however, repeat testing of some of the study patients identified three limitations of the plasma enzyme assay that is commonly used as a high throughput screening method for Fabry disease: (1) False-negative results can occur; (2) these false-negative results are not prevented by use of inhibitors of alpha-galactosidase B activity; and (3) considerable intraindividual variation in plasma alpha-galactosidase levels reduces the discriminatory power of the screening test. CONCLUSION Clinicians need to be aware that screening using plasma will fail to detect some patients with Fabry disease.