Test Catalog

Test Id : MUGS

Hexosaminidase A, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

Second-order test for diagnosing the B1 variant of Tay-Sachs disease

 

This test is not useful for testing for Sandhoff disease.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Fluorometric

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Hexosaminidase A (MUGS), S

Aliases
Lists additional common names for a test, as an aid in searching

B 1 Variant

B-1 Variant

B1 Variant

GM2 Gangliosidosis

MUGS

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Specimen Type
Describes the specimen type validated for testing

Serum

Ordering Guidance

Testing for Tay-Sachs Disease and Sandhoff Disease

The following tests are available for diagnostic and carrier testing for Tay-Sachs and Sandhoff diseases.

 

NAGR / Hexosaminidase A and Total, Leukocytes/Molecular Reflex, Whole Blood:

-This is the recommended test for carrier testing for Tay-Sachs disease and Sandhoff disease.

-Testing begins with hexosaminidase A and total enzyme analysis. If the results are consistent with an affected or carrier for Tay-Sachs disease or Sandhoff disease, next-generation sequencing to detect single nucleotide and copy number variants for HEXA or HEXB, respectively, will automatically be performed on the original specimen.

-This test is appropriate for males and pregnant or nonpregnant females.

 

NAGW / Hexosaminidase A and Total Hexosaminidase, Leukocytes:

-This test can be used for diagnosis and carrier testing for Tay-Sachs disease or Sandhoff disease.

-Results for hexosaminidase A and total enzyme analysis are reported with recommendations for additional testing when appropriate. All follow-up testing must be ordered separately on new specimens.

-This test is appropriate for males and pregnant or nonpregnant females.

 

NAGS / Hexosaminidase A and Total Hexosaminidase, Serum:

-This test can be used for diagnosis and carrier testing for Tay-Sachs disease or Sandhoff disease. Results for hexosaminidase A and total enzyme analysis are reported with recommendations for additional testing when appropriate.

-If results indicate normal, indeterminate, or carrier status and the suspicion of Tay-Sachs disease remains high, MUGS / Hexosaminidase A, Serum for Tay-Sachs disease (B1 variant) can typically be added and performed on the same specimen.

-With the exception of MUGS, all follow-up testing must be ordered separately on new specimens.

-This test is not appropriate for pregnant females or women receiving hormonal contraception. This test is appropriate for males and nonpregnant females.

-This test is particularly useful when it is difficult to obtain enough blood to perform leukocyte testing (NAGR or NAGW), as may be the case with infants.

 

MUGS / Hexosaminidase A, Serum:

-This is the recommended test for diagnosis and carrier testing for the B1 variant of Tay-Sachs disease. This test will not detect Sandhoff disease.

-This test should not be ordered as a first-line test. Rather, this test should be ordered when the NAGR, NAGW, or NAGS indicate normal, indeterminate, or carrier results and the suspicion of Tay-Sachs disease remains high. In most cases, this test can be performed on the original specimen collected for NAGS.

Necessary Information

Physician's name and phone number are required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Patient should be fasting for 4 hours.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 1 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Biochemical Genetics Patient Information (T602) in Special Instructions.

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.15 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Frozen (preferred) 365 days
Refrigerated 5 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Second-order test for diagnosing the B1 variant of Tay-Sachs disease

 

This test is not useful for testing for Sandhoff disease.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Tay-Sachs and Sandhoff diseases, also referred to as GM2 gangliosidoses, are lysosomal storage disorders caused by deficiencies of the enzymes hexosaminidase A and hexosaminidase B, respectively. These isoenzymes are dimers that differ in their subunit composition. Hexosaminidase A is a heterodimer composed of 1 alpha and 1 beta subunit (alpha-beta), while hexosaminidase B is a homodimer composed of 2 beta subunits (beta-beta). The defective lysosomal degradation and the excessive accumulation of GM2 ganglioside and related glycolipids results in the development of the clinical symptomology observed in Tay-Sachs and Sandhoff diseases.

 

Tay-Sachs and Sandhoff diseases are autosomal recessive conditions. Tay-Sachs disease results from 2 variants in HEXA, which encodes for the alpha subunit of hexosaminidase and causes a deficiency of hexosaminidase A enzyme. An increased carrier frequency for Tay-Sachs disease is observed in individuals of Ashkenazi Jewish, Celtic, and French-Canadian ancestry. Patients with Sandhoff disease have 2 variants in HEXB, which encodes for the beta subunit of hexosaminidase and results in deficiencies in both hexosaminidase A and hexosaminidase B enzymes. Sandhoff disease does not exhibit an increased carrier frequency in any specific population.

 

Clinical Phenotypes:

Phenotypically, patients with Tay-Sachs and Sandhoff diseases are clinically indistinguishable. Variability is observed with respect to age of onset and clinical symptoms. Enzyme analysis is generally required to distinguish between the 2 disorders.

 

The acute infantile forms of Tay-Sachs and Sandhoff diseases typically present with progressive motor deterioration beginning at 3 to 6 months of age. Patients exhibit weakness, hypotonia, and decreasing attentiveness. Motor skills learned previously, such as crawling or sitting alone, are nearly always lost by 1 year of age. Other symptoms include rapid diminishing of vision, seizures, macrocephaly due to cerebral gliosis, and the characteristic cherry-red spot in the retina. Affected individuals typically do not survive past 5 years of age.

 

The juvenile or subacute forms often present between 2 and 10 years of age with ataxia and clumsiness. Patients develop difficulties with speech and cognition. Neurologic features progressively get worse, and death typically occurs 2 to 4 years later. 

 

Disease progression is slower in patients with chronic or adult-onset Tay-Sachs and Sandhoff diseases. Early signs and symptoms may be subtle and nonspecific, involving muscle and/or neurologic findings, often resulting in initial misdiagnoses. Affected individuals may exhibit abnormalities of gait and posture, spasticity, dysarthria, and progressive muscle wasting and weakness. Cognitive impairment, dementia, or psychiatric findings are observed in some patients. Significant clinical variability exists both between and within families.

 

Testing Options:

Several tests are available for the detection of carriers of, and individuals affected with, Tay-Sachs and Sandhoff diseases (see table below and Testing Algorithms). The recommended test for both diagnostic and carrier testing is NAGR / Hexosaminidase A and Total, Leukocytes/Molecular Reflex, Whole Blood. Testing begins with enzyme analysis and when indicated reflexes to the appropriate molecular analysis (either HEXA or HEXB gene), which includes sequencing and deletion/duplication analysis.

 

Follow-up molecular testing is recommended for all individuals with enzyme results in the carrier, possible carrier, or affected ranges. This differentiates between nondisease-causing pseudodeficiency alleles and disease-causing variants. In addition, molecular analysis allows for the facilitation of carrier testing and prenatal diagnosis for at-risk individuals.

 

Test ID

Test Name

Tay-Sachs disease

Sandhoff disease

Reflexes to molecular genetic testing

Use during pregnancy or hormonal contraception

Preferred use

Carrier

Affected

Carrier

Affected

NAGR

Hexosaminidase A and Total, Leukocytes/Molecular Reflex, Whole Blood

Yes

Yes

Yes

Yes

Yes

Yes

Diagnostic or carrier testing

NAGW

Hexosaminidase A and Total Hexosaminidase, Leukocytes

Yes

Yes

Yes

Yes

No

Yes

Diagnostic or carrier testing

NAGS

Hexosaminidase A and Total Hexosaminidase, Serum

Yes

Yes

Yes

Yes

No

No

Diagnostic

MUGS*

Hexosaminidase A, Serum

Yes

Yes

No

No

No

No

Diagnostic, secondary only

 

*MUGS testing should be utilized only when one of the other assays indicates normal, indeterminate, or carrier results and the clinical suspicion of Tay-Sachs disease remains high.

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
Provides information to assist in interpretation of the test results

Interpretation is provided with report.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

GM2 activator deficiency (AB variant, GM2A) is a rare disorder with clinical features similar to Tay-Sachs and Sandhoff diseases; however, levels of both hexosaminidase A and B are normal. GM2 activator deficiency is not detected with this assay. Molecular genetic analysis of GM2A is available; see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Supportive Data

Regression analysis shows a linear relationship between Mayo Clinic Laboratories' MUG and 4-MUGS methods (R=0.964). A normal range of 1.23 to 2.59 U/L hexosaminidase A was determined using the 4-methylumbelliferyl-beta-D-N-acetyl-glucosamine-6-sulfate (4-MUGS) procedure on 50 normal subjects. A Tay-Sachs carrier range, based on results from 12 obligate carriers for Tay-Sachs disease, has been established tentatively as 0.58 to 1.15 U/L. This range will continue to be evaluated as more obligate carriers for Tay-Sachs disease are studied.

Clinical Reference
Recommendations for 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. Gravel RA, Kaback MM, Proia RL, Sandhoff K, Suzuki K, Suzuki K. The GM2 gangliosidoses. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed April 27, 2020. Available at: http://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225547784

3. Kaback MM, Desnick RJ. Hexosaminidase A deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated August 11, 2011. Accessed April 27, 2020. Available at: www.ncbi.nlm.nih.gov/books/NBK1218/

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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.(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 derivatives of beta-N-acetylglucosamine-6-sulfate and beta-N-acetylgalactosamine-6-sulfate. Am J Hum Genet. 1985 Jul;37(4):733-40; Cowan T, Pasquali M: Laboratory Investigations of Inborn Errors of Metabolism. In: Sarafoglou K, Hoffman GF, Roth KS eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monthly

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

30 to 45 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

30 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) 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 US 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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83080

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports