Gaucher Disease, Mutation Analysis, GBA
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Gaucher disease is a relatively rare lysosomal storage disorder resulting from a deficiency of beta-glucocerebrosidase. Mutations within the beta-glucocerebrosidase gene (GBA) cause the clinical manifestations of Gaucher disease. There are 3 major types of Gaucher disease: nonneuropathic (type 1), acute neuropathic (type 2), and subacute neuropathic (type 3). Type 1 Gaucher disease occurs most frequently and is the presentation commonly found among Ashkenazi Jewish patients. The carrier rate of Gaucher disease in the Ashkenazi Jewish population is 1/18.
Type 1 disease does not involve nervous system dysfunction; patients display anemia, low blood platelet levels, massively enlarged livers and spleens, lung infiltration, and extensive skeletal disease. The clinical variability in type 1 disease is large, with some patients exhibiting severe disease and others very mild disease.
Eight GBA mutations, including the N370S mutation found most commonly in the Ashkenazi Jewish population, are included in this test: delta 55bp, V394L, N370S, IVS2+1, 84GG, R496H, L444P, and D409H. This testing panel provides a 95% detection rate for the Ashkenazi Jewish population and up to a 60% detection rate for the non-Ashkenazi Jewish population. Alternatively, full gene sequencing is available to evaluate for mutations in all coding regions and exon/intron boundaries of the GBA gene by ordering GBAMS / Gaucher Disease, Full Gene Analysis.
Confirmation of a suspected clinical diagnosis of Gaucher disease
Carrier testing for individuals of Ashkenazi Jewish ancestry or who have a family history of Gaucher disease
Prenatal diagnosis in at-risk pregnancies
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the mutations that cause Gaucher disease. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Beutler E, Grabowski GA: Glucosylceramide lipidoses: Chpt 146: Gaucher disease. In The Metabolic Basis of Inherited Disease. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company, 1994
2. Gaucher Disease, Current Issues in Diagnosis and Treatment. Technology Assessment Conference Program and Abstracts, National Institutes of Health, Bethesda, MD, February 27-March 1, 1995
3. Charrow J, Andersson HC, Kaplan P, et al: The Gaucher Registry: Demographics and disease characteristics of 1,698 patients with Gaucher Disease. Arch Int Med 2000;160:2835-2843
4. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening individuals of Ashkenazi Jewish descent. Genet Med 2008;10(1):54-56