Sorted By Test Name - Mayo Medical Laboratories

TSD
82588
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Gravel RA, Kaback MM, Proia RL, et al: The GM2 gangliosidosis. In The
Metabolic and Molecular Bases of Inherited Disease. 8th 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
Tay-Sachs Disease, Mutation Analysis, HEXA
Clinical Information: Tay-Sachs disease is caused by an absence of hexosaminidase (Hex A)
enzyme activity, which results in the accumulation of the sphingolipid GM2 ganglioside. Mutations
within the alpha subunit of the hexosaminidase A gene, HEXA, cause the clinical manifestations
associated with Tay-Sachs disease (TSD). 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 of this condition include progressive neurodegeneration, seizures, and blindness
leading to total incapacitation and death. Other types of TSD (eg, subacute and adult onset) are
characterized by later ages of onset and death. The symptoms and severity of disease vary widely. TSD is
inherited in an autosomal recessive manner. The carrier frequency for TSD disease in the Ashkenazi
Jewish population is 1/31. This panel tests for the 3 common mutations in the Ashkenazi Jewish
population: 1278insTATC, G269S, and IVS12+1G->C. When performed in conjunction with
hexosaminidase A biochemical testing, the mutation detection rate using this assay is approximately 99%.
Also included in this analysis are the mutations IVS9+1G->A and 7.6 kbdel 5'UTR-IVS+1 that are
over-represented in individuals of Celtic or French Canadian ancestry, respectively. A common cause of
false-positive carrier screening by enzyme analysis, particularly among individuals of non-Ashkenazi
Jewish descent, is due to the presence of a pseudodeficiency allele, either R247W or R249W. These
sequence variations are not associated with disease, but result in the production of a hexosaminidase A
enzyme with decreased activity towards the artificial substrate used in the enzyme assay. Both
pseudodeficiency alleles are evaluated for by this panel. The recommended first-tier test to screen for
TSD is biochemical analysis measuring hexosaminidase enzyme activity, NAGW/8775 Hexosaminidase
A and Total Hexosaminidase, Leukocytes. Molecular tests form the basis of confirmatory diagnostic or
carrier testing. See Tay-Sachs Disease Carrier Testing Protocol in Special Instructions for additional
information. 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 diagnostic strategy. Alternatively, full gene
sequencing is available to evaluate for mutations in all coding regions and exon/intron boundaries of the
HEXA gene by ordering HEXMS/89278 Tay-Sachs Disease, HEXA Gene, Full Gene Analysis.
Useful For: Carrier testing of individuals of Ashkenazi Jewish ancestry or who have a family history of
Tay-Sachs disease Determining carrier status for individuals with enzyme activity within the carrier or
equivocal ranges Prenatal diagnosis for at-risk families Confirmation of suspected clinical diagnosis of
Tay-Sachs disease in individuals of Ashkenazi Jewish ancestry
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Gravel RA, Kaback MM, Proia RL, et al: The GM2 gangliosidosis. In The
Metabolic and Molecular Bases of Inherited Disease. Eigth edition. Edited by CR Scriver, AL Beaudet,
WS Sly, et al. New York, McGraw-Hill Book Company, available at www.ommbid.com Accessed
3-18-10 2. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening individuals of Ashkenazi Jewish
descent. Genet Med 2008;10(1):54-56
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