Use to diagnose GD only; not accurate for carrier screening
Gaucher disease (GD) is a lysosomal storage disease most often affecting individuals of Ashkenazi Jewish (AJ) descent. GD type 1 is the most common form with symptoms ranging from mild to severe. Symptoms include hepatosplenomegaly, anemia, thrombocytopenia, lung disease, and bone abnormalities. Symptoms of type 1 can appear anytime from childhood to adulthood. GD types 2 and 3 are neuronopathic forms differentiated mainly by disease progression and involve the central nervous system with life-threatening problems that typically appear in early infancy. Symptoms of types 2 and 3 also include eye abnormalities, seizures, and damage to the brain. Testing is used for prepregnancy carrier screening or for diagnostic testing in individuals suspected of having GD.
- ~1 in 57,000 to 1 in 75,000 in general population
- GD type 1 estimated at 1 in 855 in individuals of AJ descent
Age of Onset
- Type 1: childhood/adulthood
- Type 2: typically before age 2, with death by age 2-4
- Type 3: typically in childhood, but survival into third or fourth decade
GD affects lysosomal storage and has extreme symptom variability, ranging from perinatal lethality to asymptomatic individuals.
- Type 1
- Type 2 (acute neuronopathic)
- Primary central nervous system (CNS) involvement with rapidly progressive course
- Type 3 (subacute/chronic)
- Primary CNS involvement with slowly progressive course
- GBA sequencing: Long range PCR followed by bidirectional sequencing of all coding regions and intron-exon boundaries of the GBA gene
- GBA 8 Variants: Polymerase chain reaction (PCR) and fluorescence monitoring
- Targeted variants: c.115+1G>A; c.84dupG, p.L29Afs; c.1226A>G, p.N409S; c.1263_1317del55; c.1297G>T, p.V433L; c.1342G>C, p.D448H; c.1448T>C, p.L483P; and c.1604G>A, p.R535H
Test Sensitivity and Specificity
Analytical Sensitivity and Specificity
- Diagnostic errors can occur due to rare sequence variations.
- Regulatory region variants, deep intronic variants, large deletions/duplications/insertions, gene conversion events and complex gene rearrangements may not be detected.
Meikle PJ, Hopwood JJ, Clague AE, et al. Prevalence of lysosomal storage disorders. JAMA. 1999;281(3):249-254.
Biegstraaten M, van Schaik IN, Aerts JMFG, et al. 'Non-neuronopathic' Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature. J Inherit Metab Dis. 2008;31(3):337-349.