Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

NAGS
8774
disease carrier identification. Mol Genet Metab 2006 Feb;87(2):122-127 3. Kaback MM:
Hexosaminidase A Deficiency. Available from
www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tay-sachs Reviewed May 19, 2006 4.
Neudorfer O, Pastores GM, Zeng BJ, et al: Late-onset Tay-Sachs disease: phenotypic characterization
and genotypic correlations in 21 affected patients. Genet Med 2005 Feb;7(2):119-123 5. Sutton VR:
Tay-Sachs disease screening and counseling families at risk for metabolic disease. Obstet Gynecol Clin
North Am 2002 Jun;29(2):287-296 6. D'Souza G, McCann CL, Hedrick J, et al: Tay-Sachs disease
carrier screening: a 21-year experience. Genet Test 2000;4(3):257-263
Hexosaminidase A and Total Hexosaminidase, Serum
Clinical Information: Sandhoff disease and Tay-Sachs disease both belong to a subset of lysosomal
storage disorders classified as GM2 gangliosidoses. These diseases are caused by 2 different enzyme
deficiencies, but both diseases result in an accumulation of GM2 gangliosides in the lysosomes of cells,
particularly in neurons. The clinical presentation for both diseases is identical. In general, individuals with
either condition begin to develop normally, but then present with progressive weakness, hypotonia,
increased startle response, progressive neurodegeneration, spasticity, and blindness; death typically occurs
by 4 years of age. Sandhoff disease is an autosomal recessive condition resulting from 2 mutations in the
HEXB gene on 5q13, which encodes for the beta subunit of hexosaminidase. Individuals with Sandhoff
disease have deficiencies in both hexosaminidase A and hexosaminidase B. Enzymatic testing can be used
for diagnostic purposes, but individuals with possible carrier status for Sandhoff disease must be
confirmed with molecular sequence analysis of the HEXB gene. Unlike Tay-Sachs disease, Sandhoff does
not have an increased carrier frequency in individuals with Ashkenazi Jewish ancestry. Tay-Sachs disease
is an autosomal recessive condition resulting from 2 mutations in the HEXA gene on 15q23-24, which
encodes for the alpha subunit of hexosaminidase. Individuals with Tay-Sachs disease have a deficiency in
hexosaminidase A, though those that have higher residual enzyme activity may have a milder clinical
presentation with a later age of onset. The acute infantile form typically presents with progressive motor
deterioration beginning at 3 to 6 months of age and death typically occurs by 4 years of age. The juvenile
or subacute form often presents with ataxia and incoordination between 2 and 10 years of age with
progressive worsening of symptoms and death typically 2 to 4 years later. The chronic or adult-onset
subtype may present with motor weakness or psychiatric manifestations in adulthood. The carrier
frequency of Tay-Sachs disease is increased in the Ashkenazi Jewish population (1/31). There are 3 null
alleles with increased frequency in the Ashkenazi Jewish population that in either homozygous or
compound heterozygous state are known to be associated with classical Tay-Sachs disease
(1278insTATC, G269S, IVS12+1G->C). The G269S allele results in a higher residual enzyme activity
and in either a homozygous or compound heterozygous state results in the adult-onset form of Tay-Sachs
disease. In addition, IVS9+1G->A and 7.6 kbdel 5'UTR-IVS+1 are mutations 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 1 of 2 pseudodeficiency alleles, 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. The molecular genetics panel offered by
Mayo Medical Laboratories includes the 7 above-mentioned mutations (TSD/82588 Tay-Sachs Disease,
Mutation Analysis, HEXA). If both partners are found to be carriers and a pregnancy is at risk for either
disease, mutations must first be identified if prenatal testing is desired. Please refer to NAGR/82943
Hexosaminidase A and Total, Leukocytes/Molecular Reflex or NAGW/8775 Hexosaminidase A and
Total Hexosaminidase, Leukocytes for carrier detection and diagnosis of Tay-Sachs disease.
Useful For: Carrier detection and diagnosis of Sandhoff disease
Interpretation: Interpretation is provided with report. See Tay-Sachs Disease Carrier Testing Protocol
in Special Instructions for additional information.
Reference Values:
TOTAL
Reference values have not been established for patients that are less than 5 years of age.
> or =5 years: 10.4-23.8 U/L
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