Test Catalog

Test Id : NAGS

Hexosaminidase A and Total Hexosaminidase, Serum

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

Carrier detection and diagnosis of Tay-Sachs disease and Sandhoff disease

 

This test is not useful for pregnant females or those treated with hormonal contraception.

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

Heat Inactivation, Fluorometric, Automated

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 and Total, S

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

B-N-Acetylglucosaminidase

Beta-N-Acetylglucosaminidase

GM2 Gangliosidosis

Hex A Deficiency

Hex B Deficiency

Hexosaminidase A Deficiency

Hexosaminidase B Deficiency

Hexosaminidase, Total

Sandhoff Carrier Screening

Sandhoff Carrier Testing

Sandhoff Disease

Sandhoff Disease Carrier Screening

Tay Sachs Disease

Tay-Sachs Disease Testing

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):

-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, 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.

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

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

0.5 mL

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

Gross hemolysis OK
Gross lipemia OK
Gross icterus Reject

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) 30 days
Refrigerated 7 days

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

Carrier detection and diagnosis of Tay-Sachs disease and Sandhoff disease

 

This test is not useful for pregnant females or those treated with hormonal contraception.

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 non-disease 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.

HEXOSAMINIDASE TOTAL

< or =15 years: > or =20 nmol/min/mL

> or =16 years: 10.4-23.8 nmol/min/mL

 

HEXOSAMINIDASE PERCENT A

< or =15 years: 20-90%

> or =16 years: 56-80%

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.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Delnooz CCS, Lefeber DJ, Langemeijer SMC, et al: New cases of adult-onset Sandhoff disease with a cerebellar or lower motor neuron phenotype. J Neurol Neurosurg Psychiatry. 2010 Sep;81(9):968-972

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 October 06, 2021. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225547784

3. Toro C, Shirvan L, Tifft C. HEXA Disorders. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated October 1, 2020. Accessed August 17, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1218/

4. Hall P, Minnich S, Teigen C, Raymond K: Diagnosing lysosomal storage disorders: the GM2 gangliosidoses. Curr Protoc Hum Genet. 2014 Oct 1;83:17.16.1-8. doi: 10.1002/0471142905.hg1716s83

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 hexosaminidases are among the more active of the lysosomal enzymes, which hydrolyze derivatives of beta-D-N-acetylglucosamine and beta-D-N-acetylgalactosamine. Natural substrates are certain sphingolipids (ie, GM2) in which acetylgalactosamine is the terminal monosaccharide. The 2 hexosaminidase isoenzymes, A and B, differ in their electrophoretic mobility and heat stability. Hexosaminidase A moves toward the anode and is heat labile, while hexosaminidase B moves toward the cathode and is heat stable.

 

The procedure is performed using an automated pipetting station and a spectrophotometer. The substrate used is 4-methylumbelliferyl-N-acetyl-beta-D-glucopyranoside (4-MUF-acetamido-2-deoxy-beta-D-glucopyranoside) from which the fluorescent compound, 4-methylumbelliferone, is liberated by both hexosaminidases.

 

The sample is mixed with citrate phosphate buffer and mixture is separated into 2 tubes. One tube stays at ambient temperature and the other is heated at 51.5 degrees C for 15 minutes. On the automated pipetting station, sample and substrate are pipetted into a microtiter test tube located in a 37 degree C waterbath. The hexosaminidase A fraction is destroyed in the heated sample, leaving only hexosaminidase B to react with the substrate. The unheated sample provides the total hexosaminidase (A and B). The reaction is stopped with glycine after the 30-minute incubation. Sample intensities are compared to that of a 4-methylumbelliferone standard curve to quantitate both the total and the B fraction. The percentage of the A fraction that was inactivated by heating is calculated based on these results. The difference in heat inactivation is used to fractionate hexosaminidase activities.(O'Brien JF, Burtis CA, Ashwood ER: Lysosomal storage diseases. In: Tietz Textbook of Clinical Chemistry. 2nd ed. WB Saunders Company; 1994:2149-2160; Cowan T, Pasquali M: Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KD, 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.

Thursday

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.

8 to 15 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 x 2

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
NAGS Hexosaminidase A and Total, S 87545-0
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
27612 Hexosaminidase Total, S 1956-2
27613 Hexosaminidase Percent A, S 12914-8
27216 Interpretation (NAGS) 59462-2
27218 Reviewed By 18771-6

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 | Create a 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