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

MUGS
80350
2 0.70-3.49 Positive
3 3.50-17.4 Positive
4 17.5-49.9 Strongly positive
5 50.0-99.9 Strongly positive
6 > or =100 Strongly positive Reference values
apply to all ages.
Clinical References: Homburger HA: Allergic diseases. In Clinical Diagnosis and Management
by Laboratory Methods. 21st edition. Edited by RA McPherson, MR Pincus. New York, WB Saunders
Company, 2007, Chapter 53, Part VI, pp 961-971
Hexosaminidase A (MUGS), Serum
Clinical Information: Tay-Sachs disease (TSD), variant B1 is a rare variant of the gangliosidoses, a
group of lysosomal storage disorders characterized by the accumulation of GM2 gangliosides in neurons
due to deficient hexosaminidase A (Hex A) enzyme activity. Hex A is a heterodimer, consisting of 1 alpha
and 1 beta subunit. The other major hexosaminidase (Hex B) consists of 2 beta subunits and is not capable
of hydrolyzing GM2 gangliosides. TSD variant B1 is a rare variant that has an increased frequency in
individuals with Portuguese ancestry. The most common mutation causing the B1 variant is the R178H in
the HEXA gene. This mutation results in the synthesis and assembly of an alpha subunit that renders the
enzyme unable to hydrolyze its physiological substrate (ie, GM2 ganglioside), yet capable of hydrolyzing
some synthetic substrates used to assess Hex A activity, such as 4-methylumbelliferyl
N-acetylglucosamine (MUG). Using the MUG substrate, the Hex A activity of individuals with B1 variant
mutation(s) appears to be within or near the normal range. Conversely, the B1 variant enzyme is unable to
hydrolyze the sulfated MUG derivative MUGS (4-methylumbelliferyl N-acetylglucosamine 6-sulphate).
Therefore, distinguishing the B1 variant from normal requires the use of MUGS substrate. In general, the
clinical presentation of the B1 variant typically presents with a later age of onset. Individuals who are
compound heterozygotes for the B1 variant with a null allele typically present with a juvenile
presentation. An individual who is homozygous for the B1 variant typically presents with a later onset and
a milder, chronic clinical presentation. See Hexosaminidase: Subunit Location of the Synthesis and
Substrate of Dimeric Isoenzymes of Hexosaminidase in Multimedia. Refer to Carrier Testing for
Tay-Sachs Disease and Other GM2 Gangliosidosis Variants: Supplementing Traditional Biochemical
Testing with Molecular Methods, MML Communique 2004 Jul;29(7) for more information regarding
diagnostic strategy (article is available online at
MayoMedicalLaboratories.com/media/articles/communique/mc2831-0704.pdf).
Useful For: A second-order test for diagnosing the B1 variant of Tay-Sachs disease This test should be
ordered when the patient exhibits Tay-Sachs symptoms, but has tested as normal, ambiguous, or carrier by
either NAGS/8774 Hexosaminidase A and Total Hexosaminidase, Serum or NAGW/8775
Hexosaminidase A and Total Hexosaminidase, Leukocytes.
Interpretation: Interpretation is provided with report. The B1 mutation results in depressed Hex A
isoenzyme (as assayed by 4-MUGS), whereas it reacts normally to 4-MUG. Follow-up testing using
leukocytes is recommended for ambiguous results.
Reference Values:
1.23-2.59 U/L (normal)
1.16-1.22 U/L (indeterminate)
0.58-1.15 U/L (carrier)
Clinical References: 1. Tutor JC: Biochemical characterization of the GM2 gangliosidosis B1
variant. Braz J Med Biol Res 2004 Jun;37(6):777-783 2. Bayleran J, Hectman P, Saray W: Synthesis of
4-methylumbelliferyl-beta-D-N-acetylglucosamine-6-sulfate and its use in classification of GM2
gangliosidosis genotypes. Clin Chim Acta 1984;143:73-89 3. Inui K, Wenger DA: Usefulness of
4-methylumbeliferyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside for the diagnosis of GM2
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