Acid β-Glucosidase (Gaucher Disease)
Related Gene(s): GBA
Gaucher disease is one of the most common lysosomal storage diseases with a prevalence of 1 in 40,000 to 1 in 50,000 people in the general population. It is much more frequent (as high as 1 in 850 people) in Ashkenazi Jewish individuals, due to the founder mutations. This autosomal recessive disorder is caused by mutations in the GBA gene and deficiency of glucocerebrosidase (acid β-glucosidase). As a result, glucosylcerebrosie (glucosylceramide) and glucosylsphinogosine accumulate in cells of the monocyte or macrophage lineage, including the spleen, liver, and bone marrow.
The signs and symptoms of this condition vary widely among affected individuals. Type 1 is non-neuronopathic and the most common form of Gaucher disease. It has a variable clinical phenotype, ranging from asymptomatic to severe. The classic presentations in childhood include massive hepatosplenomegaly, pancytopenia, and severe skeletal abnormalities. The bony problems and episodic painful bone crises usually occur later than the development of visceral enlargements. Erlenmeyer flask deformity of the distal femur is a characteristic radiological finding of Gaucher bone disease. In addition to the visceral involvements, type 2 is a fatal neurodegenerative disorder of infancy. Type 3 has a severity intermediate between type 1 and type 2.
Diagnosis of Gaucher disease can be established by demonstration of reduced acid β-glucosidase activity in leukocytes or cultured fibroblasts (less than 15% of normal). The acid β-glucosidase activity is measured with a lysate from the patient’s white blood cells (WBC) by a liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. The clinical purpose of this assay is for the diagnosis of Gaucher disease. This enzyme assay is not used for the carrier identification. Carrier testing can be accomplished through molecular analysis of the GBA gene.
To order prenatal testing, please contact our laboratory at 212-241-7518.
- Anticoagulated blood: 5-10 mL in sodium heparin tube (green top) or 1-2 leukocyte pellets
- Ship whole blood at room temperature; sample must be received within 72 hours of collection
- Ship leukocyte pellet(s) frozen on dry ice
- 7 days