Interpretive Handbook

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 the 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 respect to age of onset and clinical presentation. Type 1 is the most common type, representing 95% of all cases, and is generally characterized by bone disease, hepatosplenomegaly, anemia and thrombocytopenia, coagulation abnormalities, lung disease, and no CNS involvement. Type 2 typically has a very severe progression with onset prior to 2 years, with neurologic disease, hepatosplenomegaly, and lung disease, 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.

Treatment is available in the form of enzyme replacement therapy and/or substrate reduction therapy for types 1 and 3. Individuals with type 3 may benefit from bone marrow transplantation. Currently, only supportive therapy is available for type 2.

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 900. Types 2 and 3 both have an incidence of approximately 1 in 100,000 in the general population.

A diagnostic workup for Gaucher disease may demonstrate the characteristic finding of "Gaucher cells" on bone marrow examination. Reduced or absent enzyme activity of acid beta-glucosidase is diagnostic. A targeted mutation panel may allow for detection of disease-causing mutations in affected patients (GAUW/81235 Gaucher Disease, Mutation Analysis, GBA). In addition, full sequencing of the GBA gene allows for detection of disease-causing mutations in affected patients in whom a targeted mutation panel identifies only a single mutation.

Diagnosis of Gaucher disease

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 determine carrier status, order GAUW/81235 Gaucher Disease, Mutation Analysis, GBA.

Interfering factors include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, and exposure of the specimen to temperature extremes (freezing or >30 degrees C).

3.80-8.70 U/g of cellular protein

1. Martins AM, Valadares ER, Porta G, et al: Recommendations on diagnosis, treatment, and monitoring for Gaucher disease. J Pediatr 2009 Oct;155(4 Suppl):S10-S18

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

3. Pastores GM, Hughes DA: Gaucher disease. In GeneReviews. Seattle: University of Washington, Seattle; 1993-. Edited by RA Pagon TD Bird, CR Dolan, et al: 2000 Jul 27 [Updated 2011 Jul 21]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1269/