Test ID: BGLT
Beta-Glucosidase, Fibroblasts

Diagnosis of Gaucher disease

Not recommended for carrier detection; instead order GAUW/81235 Gaucher Disease, Mutation Analysis, GBA.

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by reduced or absent acid beta-glucosidase (glucocerebrosidase) enzyme activity. Absent or reduced activity of this enzyme results in accumulation of undigested materials (primarily in the lysosomes) and interferes with the normal functioning of cells.

Clinical features and severity of symptoms are widely variable within Gaucher disease, but in general, the disorder is characterized by bone disease, hepatosplenomegaly, and may have central nervous system (CNS) involvement. There are 3 clinical subtypes of the disorder that vary with regard to age of onset and clinical presentation. Type 1 is by far the most common type (95% of all cases) and generally classified by bone disease, hepatosplenomegaly, anemia, lung disease, and no CNS involvement. Type 2 typically has a very severe progression with onset prior to 2 years, disease affecting the brain, spleen, liver, and lungs, with death usually between 2 and 4 years due to lung failure. Individuals with type 3 may have onset prior to 2 years of age, but the progression is not as severe and they may survive into the third and fourth decade. In addition, there is a perinatal lethal form associated with skin abnormalities and nonimmune hydrops fetalis and a cardiovascular form presenting with calcification of the aortic and mitral valves, mild splenomegaly, and corneal opacities.

The incidence of type 1 ranges from 1 in 20,000 to 1 in 200,000 in the general population, but is much more frequent among Ashkenazi Jews with an incidence between 1 in 400 to 1 in 600. Types 2 and 3 are pan ethnic, each with an incidence of 1 in 100,000.

A diagnostic work up for Gaucher disease may demonstrate the characteristic finding of "Gaucher cells" on bone marrow examination. Reduced or absent enzyme activity of acid beta-glucosidase in leukocytes, blood spots, and/or fibroblasts can confirm a diagnosis. A targeted mutation panel may allow for detection of disease-causing mutations in affected patients. In addition, sequencing of the GBA gene allows for detection of disease-causing mutations in affected patients in whom a targeted mutation panel identified only a single mutation.

Treatment is available in the form of enzyme replacement therapy and/or substrate reduction therapy for types 1 and 3. Partial or total splenectomy may be indicated in cases with massive splenomegaly and thrombocytopenia. Individuals with type 3 may benefit from bone marrow transplantation. Currently, only supportive therapy is available for type 2.

See Lysosomal Storage Disorders in Special Instructions.

3.80-8.70 U/g of cellular protein

Values <2.0 U/g of cellular protein are consistent with a diagnosis of Gaucher disease

Leukocytes are the preferred specimen for the diagnosis of Gaucher disease.

Carrier testing using this assay is not reliable. To detetermine carrier status, order GAUW/81235 Gaucher Disease, Mutation Analysis, GBA.

Interfering factors include:

-Lack of viable cells or bacterial contamination

-Failure to transport tissue in an appropriate media

-Excessive transport time

-Exposure of the specimen to temperature extremes (freezing or >30 degrees C)

1. Martins AM, et al: Recommendations on diagnosis, treatment, and monitoring for Gaucher disease. J Pediatr 2009 Oct;155(4 Suppl):S10-18

2. Beulter E, Grabowski GA: Gaucher disease. In The Metabolic and Molecular Basis of Inherited Disease. Vol. 3. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill, 2001, pp 3635-3656

• Lysosomal Storage Disorders
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