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Diagnosis of Gaucher disease
Preferred specimen for diagnostic testing. Not recommended for carrier detection; instead order GAUP / 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 glucocerebroside 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 abnormal blood parameters such as decreased red blood cells (anemia) and/or platelets (thrombocytopenia), bone disease, and hepatosplenomegaly. Individuals with more severe types of Gaucher disease 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 in the first 2 years of life including 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, substrate reduction therapy, and/or chaperone 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 200,000 in the general population, but is much more frequent among Ashkenazi Jews with an incidence between 1 in 400 and 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 (GAUP / 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 (GBAZ / Gaucher Disease, Full Gene Analysis).
> or =8.7 nmol/h/mg protein
Note: Results from this assay do not reflect carrier status because of individual variation of beta-glucosidase enzyme levels. For carrier testing, order molecular test GAUP / Gaucher Disease, Mutation Analysis, GBA.
Values <8.7 nmol/h/mg protein are consistent with a diagnosis of Gaucher disease.
Carrier testing using this assay is not reliable. Use molecular test GAUP / Gaucher Disease, Mutation Analysis, GBA for this purpose.
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. Grabowski GA, Petsko GA, Kolodny EH: Chapter 146: Gaucher Disease. In Scriver’s The Online Metabolic and Molecular Basis of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill Medical Division. Accessed 3/17/2015. Available at www.ommbid.com
3. Pastores GM, Hughes DA: Gaucher disease. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. University of Washington. 2000 Jul 27 (Updated 2015 Feb 26). Accessed 3/17/2015. Available at www.ncbi.nlm.nih.gov/books/NBK1269/
4. Weinreb NJ, Andersson HC, Banikazemi M, et al: Prevalence of type 1 Gaucher disease in the United States. Arch Intern Med 2008;168:326-328