Hexosaminidase A (MUGS), Serum
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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.
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
This test should only be used to investigate for the rare B-1 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. If you have questions, please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 and ask for the on-call biochemical genetics counselor.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Fluorometric Manual Method Using 4-MUGS Substrate
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Hexosaminidase A (MUGS), S
B 1 Variant
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test is not valid for pregnant females.
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 1 mL
Collection Instructions: Fasting (4 hours)
Additional Information: Physician's name and phone number are required.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross OK
Mild OK; Gross OK
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Serum||Frozen (preferred)||365 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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).
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.
1.23-2.59 U/L (normal)
1.16-1.22 U/L (indeterminate)
0.58-1.15 U/L (carrier)
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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
If carrier screening for Tay-Sachs or Sandhoff disease is desired in a pregnant female and testing was not performed prior to pregnancy, please refer to NAGR/82943 Hexosaminidase A and Total, Leukocytes/Molecular Reflex or NAGW/8775 Hexosaminidase A and Total Hexosaminidase, Leukocytes for testing on the patient or partner.
Note: Serum assay results are not valid on pregnant females and will not be run. The recommended test for Tay-Sachs carrier screening (regardless of gender or pregnancy status) is NAGR/82943 Hexosaminidase A and Total, Leukocytes/Molecular Reflex.
Because of the nature of Tay-Sachs screening, it is imperative that abnormal results reach the physician promptly so that the couple can be provided with genetic counseling and that additional specimens can be collected quickly, if necessary. Therefore, Mayo Medical Laboratories requires the name and phone number of the ordering physician to accompany the specimen.
Regression analysis shows a linear relationship between our MUG and 4-MUGS methods (R=0.964). On the basis of results from 50 normal subjects, we determined a normal range of 1.23 U/L to 2.59 U/L Hex A using the 4-MUGS procedure. A Tay-Sachs carrier range, based on results from 12 obligate carriers for Tay-Sachs disease, has been established tentatively as 0.58 U/L to 1.15 U/L. This range will continue to be evaluated as more obligate carriers for Tay-Sachs disease are studied.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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 gangliosidoses in leukocytes. Clin Genet 1984;26:318-321
4. Ben-Yoseph Y, Reid JE, Shapiro B, Nadler HL: Diagnosis and carrier detection of Tay-Sachs disease: direct determination of Hexosaminidase A using 4-methylumbelliferyl derivative of beta-N-acetyl-glucosamine-6-sulfate and beta-N-acetylgalactosamine-6-sulfate. Am J Hum Genet 1985;37:733-740
5. Fuchs W, Navon R, Kaback MM, Kresse H: Tay-Sachs disease: one-step assay of beta-N-acetylhexosaminidase in serum with a sulphated chromogenic substrate. Clin Chim Acta 1983;133:253-261
Method Description Describes how the test is performed and provides a method-specific reference
The substrate, 4-methylumbelliferyl-beta-D-N-acetyl-glucosamine-6-sulfate (4-MUGS) is highly specific for hexosaminidase A with minimal hydrolysis by placental hexosaminidase and none by hexosaminidase B. Hexosaminidase A hydrolyzes the 4-MUGS substrate, producing free 4-methylumbelliferyl, which fluoresces at an alkaline pH. Hexosaminidase A activity is determined by the amount of fluorescence produced. (Yoav Ben-Yoseph J: Neurol Sci 1988;87:103-119)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Tuesday; 10:00 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
84999 (see CPT Coding in Special Instructions)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|80350||Hexosaminidase A (MUGS), S||16457-4|