Successful screening for Gaucher disease in a high-prevalence population in tabuleiro do Norte (northeastern Brazil): a cross-sectional study.

BACKGROUND: Gaucher disease (GD) is a hereditary lysosomal storage disorder characterized by the accumulation of glucosylceramide, mainly in the cells of the reticuloendothelial system, due to a deficiency of the enzyme acid β-glucosidase (GBA). Diagnosis is usually based on measurement of GBA activity in peripheral leukocytes. The purpose of this study was to evaluate the ability of screening for GBA and chitotriosidase activity using dried blood spots on filter paper (DBS-FP) to identify individuals at high risk for GD in high-risk populations such as that of Tabuleiro do Norte, a small town in Northeastern Brazil.
METHODS: Between 1 June 2007 and 31 May 2008, 740 consented residents and descendants of traditional families from Tabuleiro do Norte were submitted to screening with DBS-FP. Subjects with GBA activity < 2.19 nmol/h/mL were referred to the analysis of GBA and chitotriosidase activity in peripheral leukocytes and in plasma, respectively. Subjects at highest risk for GD (GBA activity in peripheral leukocytes < 5.6 nmol/h/mg protein) were referred to molecular analysis to confirm diagnosis.
RESULTS: Screening with DBS-FP identified 135 subjects (18.2%) with GBA activity < 2.19 nmol/h/mL, 131 of whom remained in the study. In ten of these (7.6%), GBA activity in leukocytes was 2.6-5.5 nmol/h/mg protein. Subsequent molecular analysis confirmed six cases of heterozygosity and four normals for GD.
CONCLUSION: DBS-FP assay was shown to be an effective initial GD-screening strategy for high-prevalence populations in developing regions. Diagnosis could not be established from GBA activity in leukocytes alone, but required confirmation with molecular analysis.