Screening for patients with Gaucher’s disease using routine pathology
results: PATHFINDER (ferritin, alkaline phosphatase, platelets) study
Abstract
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.