Aims: Lysosomal β-glucocerebrosidase (GBA) deficiency causes Gaucher disease (GD), a recessive disorder caused by bi-allelic mutations in GBA. The prevalence of GD is associated with ethnicity, but largely unknown and potentially underestimated in many countries. GD may manifest with organomegaly, bone involvement and neurological symptoms as well as abnormal laboratory biomarkers. This study attempted to screen for GD in patients using abnormal platelet, alkaline phosphatase (ALP) and ferritin results from laboratory databases. Methods: Electronic laboratory databases were interrogated using a 2-4 year time interval to identify from clinical biochemistry records patients with a phenotype of reduced platelets (<150x109/L) and either elevated ALP (>130iu/L) or ferritin (>150 (female) or >250µg/L(male)). The mean value over the screening window was used to reduce variability in results. A dried blood spot sample was collected for the determination of GBA activity in patients meeting these criteria. If low GBA activity was found then the concentration of the GD-specific biomarker glucosyl-sphingosine (lyso-GB1) was assayed, and the GBA gene sequenced. Results: Samples were obtained from 1058 patients; 232 patients had low GBA activity triggering further analysis. No new cases of GD with homozygosity for pathogenic variants were identified but 12 patients (1%) were identified to be carriers of a pathogenic variant in GBA. Conclusions: Pathology databases hold routine information that can be used to screen for patients with inherited errors of metabolism. However, biochemical screening using mean platelets, ALP and ferritin has a low yield for unidentified cases of Gaucher Disease.
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.