Tay-Sachs Disease, HEXA Gene, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Tay-Sachs disease (TSD) is an inherited lysosomal storage disease caused by a deficiency of the enzyme beta-hexosaminidase A. It is characterized by accumulation of GM2 gangliosides in cells of the brain and central nervous system. The HEXA gene encodes the alpha subunit of beta-hexosaminidase A and mutations in this gene cause TSD. TSD occurs in approximately 1 in 200,000 live births with a carrier frequency of 1/250 to 1/300 in the general population. The carrier frequency for this disease in individuals of Ashkenazi Jewish ancestry is 1/31.
The classic form of TSD becomes apparent in infancy when mild motor weakness is noted along with impaired visual acuity and the presence of a "startle response." Other manifestations include progressive neurodegeneration, seizures, and blindness, leading to total incapacitation and death. The subacute and adult-onset types of TSD are characterized by later ages of onset and a broad spectrum of disease symptoms and severity.
TSD is inherited in an autosomal recessive manner. Several common mutations in the HEXA gene account for 92% of disease-causing mutations in the Ashkenazi Jewish population. Testing for these mutations is available as a panel, TSD / Tay-Sachs Disease, Mutation Analysis, HEXA. In non-Ashkenazi Jewish individuals, the detection rate for the common mutations is significantly decreased. Sequencing of the entire HEXA gene detects less common disease-causing mutations.
The recommended first-tier test for TSD carrier screening and diagnosis in all patients is a biochemical test that measures hexosaminidase A activity in white blood cells, NAGW / Hexosaminidase A and Total Hexosaminidase, Leukocytes. Refer to Carrier Testing for Tay-Sachs Disease and Other GM2 Gangliosidosis Variants: Supplementing Traditional Biochemical Testing with Molecular Methods, Mayo Medical Laboratories Communique 2004 Jul;29(7) for more information regarding testing strategy.
Carrier testing of individuals for Tay-Sachs disease (TSD) when familial mutations have been previously identified
Diagnostic confirmation of TSD when familial mutations have been previously identified
Prenatal testing when 2 familial mutations have been previously identified in an affected family member
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
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order TSD / Tay-Sachs, Mutation Analysis or HEXMS / Tay-Sachs Disease, HEXA Gene, Full Gene Analysis.
Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with Tay-Sachs disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
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. Gravel RA, Kaback MM, Proia RL, et al: The GM2 gangliosidosis. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 3827-3876
2. ACOG Committee on Genetics: ACOG Committee Opinion #318; Screening for Tay-Sachs disease. Obstet Gynecol. 2005;106(4):893-894