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
Ruling out I-cell 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.
For more information see Tay-Sachs and Related Disorders Diagnostic Testing Algorithm
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.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
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.
For more information see Tay-Sachs and Related Disorders Diagnostic Testing Algorithm
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, 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
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into plastic vial.
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:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Biochemical Genetics Patient Information (T602)
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. The minimum volume is sufficient for one attempt at testing.
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
Ruling out I-cell 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.
For more information see Tay-Sachs and Related Disorders Diagnostic Testing Algorithm
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 result 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 virtually 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, Ordering Guidance, and Testing Algorithm). 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.
Table.
| 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;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 September 10, 2024. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225547784
3. Toro C, Shirvan L, Tifft C. HEXA Disorders. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1999. Updated October 1, 2020. Accessed September 10, 2024. 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;83:17.16.1-8. doi:10.1002/0471142905.hg1716s83
5. Leal AF, Benincore-Florez E, Solano-Galarza D, et al. GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies. Int J Mol Sci. 2020;21(17):6213. Published 2020 Aug 27. doi:10.3390/ijms21176213
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
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.
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
Indicates the location of the laboratory that performs the test
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 account representative. 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. It 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.
CPT codes are provided by the performing laboratory.
83080
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 |