Identification of patients with Fabry disease using routine pathology
results: PATHFINDER (eGFR) study
Abstract
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
40000-117,000 but the exact frequency is disputed depending on
ascertainment of late-onset cases and degree of female penetrance. 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 results identified 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
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/hr) and
increased Lyso-GL-3 (5.5 ng/ml) was identified and shown to be
heterozygous for a FD mutation (c.898C>T; p.L300F;
Leu300Phe). It was later confirmed 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 has a low yield
for unidentified cases of Fabry Disease.