Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study.

Aims: Lysosomal α-galactosidase A deficiency (Fabry disease (FD)) was considered an X-linked recessive disorder but is now viewed as a variable penetrance dominant trait. The prevalence of FD is 1 in 40 000-117 000 but the ascertainment of late-onset cases and degree of female penetrance makes this unclear. Its prevalence in the general population, especially in patients with abnormal renal function is unclear. This study attempted to identify the prevalence of FD in patients with abnormal renal function results from laboratory databases.

Methods: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of reduced estimated glomerular filtration rate categorised by age on one occasion or more over a 3-year time interval. Patients were recalled and a dried blood spot sample was collected for the determination of α-galactosidase A activity by fluorimetric enzyme assay in men and mass spectrometry assays of α-galactosidase A and lyso-globotriaosylceramide (lyso-GL-3) concentrations in women.

Results: Samples were obtained from 1084 patients identified with reduced renal function. No cases of FD were identified in 505 men. From 579 women, one subject with reduced α-galactosidase activity (1.5 µmol/L/h) and increased Lyso-GL-3 (5.5 ng/mL) was identified and shown to be heterozygous for a likely FD pathogenic variant (GLA c.898C>T; p.L300F; Leu300Phe). It was later confirmed that she was a relative of a known affected patient.

Conclusions: Pathology databases hold routine information that can be used to identify patients with inherited errors of metabolism. Biochemical screening using reduced eGFR alone has a low yield for unidentified cases of Fabry Disease.