Diagnosis of lysosomal storage disorders: Gaucher disease.

Diagnosis of lysosomal storage disorders: Gaucher disease. Curr Protoc Hum Genet. 2014;82:17.15.1-6 Authors: Johnson BA, Dajnoki A, Bodamer O Abstract Gaucher Disease (GD) is a progressive lysosomal storage disorder caused by deficiency of glucocerebrosidase (GBA). The clinical phenotype follows a spectrum ranging from severe early-onset to milder late-onset disease. The absence of neurological involvement defines GD type I, whereas neuronopathic features define GD type II and III. Early diagnosis may be important for timely initiation of enzyme replacement therapy to prevent disease complications, although the enzyme does not cross the blood brain barrier. Diagnosis of GD can be readily achieved by analysis of GBA in leukocytes, fibroblasts, and/or dried blood spots using fluorometric, microfluidic or mass spectrometry-based assays. Low GBA activities are typically confirmed through molecular analysis of the GBA gene. GBA analysis in dried blood spots may be attractive for high-throughput screening of at-risk individuals and/or newborn infants. The method detailed in this unit is based on GBA analysis by tandem mass spectrometry following incubation of dried blood spots with the GBA-specific substrate D-glucosyl-β1-1'-N-dodecanoyl-D-erythro-sphingosine [C12-glucocerebroside (C36 H69 NO8 )] and internal standard N-myristoyl-D-erythro-sphingosine [C14-ceramide (C32 H63 NO3 )]. GBA activities in more than 2,000 newborn infants showed ...
Source: Current Protocols in Human Genetics - Category: Genetics & Stem Cells Tags: Curr Protoc Hum Genet Source Type: research