Test Id : NAGR
Hexosaminidase A and Total, Leukocytes/Molecular Reflex, Whole Blood
Useful For
Suggests clinical disorders or settings where the test may be helpful
Carrier detection and diagnosis of Tay-Sachs disease
Carrier detection and diagnosis of Sandhoff disease
Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| G145 | Hereditary Custom Gene Panel Tier 1 | No, (Bill Only) | No |
| G146 | Hereditary Custom Gene Panel Tier 2 | No, (Bill Only) | No |
| G147 | Hereditary Custom Gene Panel Tier 3 | No, (Bill Only) | No |
| G148 | Hereditary Custom Gene Panel Tier 4 | No, (Bill Only) | No |
| G149 | Hereditary Custom Gene Panel Tier 5 | No, (Bill Only) | No |
| G150 | Hereditary Custom Gene Panel Tier 6 | No, (Bill Only) | No |
| CGPH | Custom Gene Panel, Hereditary | Yes | No |
| HEXBZ | HEXB Gene, Full Gene Analysis | Yes | No |
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If result interpretation is consistent with carrier, indeterminate, or affected for Tay-Sachs disease or Sandhoff disease, then next-generation sequencing to detect single nucleotide and copy number variants for HEXA or HEXB, respectively, will be performed at an additional charge.
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/Semiautomated
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
Hexosaminidase A
Sandhoff Carrier Screening
Sandhoff Disease
Sandhoff Disease Carrier Screening
Tay Sachs Carrier Screening
Tay Sachs Disease
Tay Sachs Disease Carrier Screening
Tay Sachs Enzyme Testing with Molecular Reflex
Tay-Sachs Carrier Screening
Tay-Sachs Disease (TSD)
Tay-Sachs Disease Carrier Screening
Tay-Sachs Enzyme Testing With Molecular Reflex
TSD (Tay-Sachs Disease)
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If result interpretation is consistent with carrier, indeterminate, or affected for Tay-Sachs disease or Sandhoff disease, then next-generation sequencing to detect single nucleotide and copy number variants for HEXA or HEXB, respectively, will be performed at an additional charge.
For more information see Tay-Sachs and Related Disorders Diagnostic Testing Algorithm
Specimen Type
Describes the specimen type validated for testing
Whole Blood ACD
Ordering Guidance
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.
Shipping Instructions
For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerated within 6 days of collection to be stabilized. Collect specimen Monday through Thursday only and not the day before a holiday. Specimen should be collected and packaged as close to shipping time as possible.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Container/Tube:
Preferred: Yellow top (ACD solution B)
Acceptable: Yellow top (ACD solution A)
Specimen Volume: 6 mL
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
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.
5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | 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 |
|---|---|---|---|
| Whole Blood ACD | Refrigerated (preferred) | 6 days | YELLOW TOP/ACD |
| Ambient | 6 days | YELLOW TOP/ACD |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Carrier detection and diagnosis of Tay-Sachs disease
Carrier detection and diagnosis of Sandhoff disease
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
If result interpretation is consistent with carrier, indeterminate, or affected for Tay-Sachs disease or Sandhoff disease, then next-generation sequencing to detect single nucleotide and copy number variants for HEXA or HEXB, respectively, will be performed at an additional charge.
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). This test is the recommended test for both diagnostic and carrier testing. Testing begins with enzyme analysis and when indicated reflexes to the appropriate molecular analysis (either HEXA or HEXB gene), which includes next-generation sequencing to detect single nucleotide and copy number variants.
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/mg
> or =16 years: 16.4-36.2 nmol/min/mg
HEXOSAMINIDASE PERCENT A
< or =15 years: 20-80% of total
> or =16 years: 63-75% of total
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
A small percentage (<0.5%) of carriers may exhibit normal hexosaminidase A activity and will not be detected by this method.(1)
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. Triggs-Raine BL, Feigenbaum ASJ, Natowicz M, et al. Screening for carriers of Tay-Sachs disease among Ashkenazi Jews-A comparison of DNA-based and enzyme-based tests. N Engl J Med. 1990323(1):6-12
2. 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
3. Vallance H, Morris TJ, Coulter-Mackie M, Lim-Stelle J, Kaback M. Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification. Mol Genet Metab. 2006;87(2):122-127
4. 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/
5. Neudorfer O, Pastores GM, Zeng BJ, Gianutsos J, Zaroff CM, Kolodny EH. Late-onset Tay-Sachs disease: phenotypic characterization and genotypic correlations in 21 affected patients. Genet Med. 2005;7(2):119-123
6. Sutton VR. Tay-Sachs disease screening and counseling families at risk for metabolic disease. Obstet Gynecol Clin North Am. 2002;29(2):287-296
7. Gravel RA, Kaback MM, Proia RL, Sandhoff K, Suzuki K, Suzuki K: The GM2 gangliosidoses. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill. Accessed September 10, 2024. Available at http://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225547784
8. D'Souza G, McCann CL, Hedrick J, et al. Tay-Sachs disease carrier screening: a 21-year experience. Genet Test. 2000;4(3):257-263. doi:10.1089/10906570050501470
Method Description
Describes how the test is performed and provides a method-specific reference
Leukocyte hexosaminidase A and total hexosaminidase are estimated using a semiautomated modification of the method of O'Brien, et al (1970) with further specific recommendations on specimen preparation as outlined by the International Tay-Sachs Disease Testing Quality Control and Data Collection Center.(O'Brien JS, Okada S, Chen A, Fillerup DL: Tay-Sachs disease: detection of heterozygotes and homozygotes by hexosaminidase assay. N Engl J Med. 1970;283[1]:15-20; 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)
Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the gene analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction based quantitative method is performed to test for the presence of deletions and duplications in the gene analyzed.
There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.(Unpublished Mayo method)
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.
Preanalytical processing occurs Monday through Saturday.
Assay is performed: Friday
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 x2
81406 (if appropriate)
81479 (if appropriate)
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 |
|---|---|---|
| NAGR | Hexosaminidase A and Tot, WBC/Mole | 87543-5 |
| 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.
|
|---|---|---|
| 8775 | Hexosaminidase Total, WBC | 24075-4 |
| 2294 | Hexosaminidase Percent A, WBC | 23825-3 |
| 2284 | Interpretation (NAGW) | 59462-2 |
| 35029 | Reviewed By | 18771-6 |