Test ID: NAGS
Hexosaminidase A and Total Hexosaminidase, Serum
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Carrier detection and diagnosis of Sandhoff disease
Carrier detection and diagnosis of Tay-Sachs disease (testing option-this is not the recommended test)
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Useful for carrier detection and diagnosis of Sandhoff disease. Please refer to NAGR/82943 Hexosaminidase A and Total, Leukocytes/Molecular Reflex or NAGW/8775 Hexosaminidase A and Total Hexosaminidase, Leukocytes for carrier detection and diagnosis of Tay-Sachs disease.
See Tay-Sachs Disease Carrier Testing Protocol in Special Instructions.
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
Method Name A short description of the method used to perform the test
Heat Inactivation, Fluorometric, Automated
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
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
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.
Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Additional Information:
1. Serum assay results are not valid on pregnant females and will not be run. If carrier screening for Tay-Sachs or Sandhoff disease is desired in a pregnant female and testing was not performed prior to pregnancy, 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 and partner.
2. The recommended test for Tay-Sachs carrier screening (regardless of gender or pregnancy status) is NAGR/82943 Hexosaminidase A and Total, Leukocytes/Molecular Reflex.
Forms:
1. 1. 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.
2. 2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
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.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross OK |
| Lipemia | Mild OK; Gross OK |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Frozen (preferred) | 30 days |
| Refrigerated | 7 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Tay-Sachs disease and Sandhoff disease are lysosomal storage disorders, also referred to as GM2 gangliosidoses, 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 Disease:
Tay-Sachs disease is caused by a deficiency of hexosaminidase A due to a defect in the alpha subunit. This autosomal recessive condition results from 2 mutations in the HEXA gene, which encodes for the alpha subunit of hexosaminidase. Individuals with Tay-Sachs disease have a deficiency in hexosaminidase A; those with higher residual enzyme activity may have a milder clinical presentation with a later age of onset.
The acute infantile form typically presents 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 age 1. Other symptoms include rapid diminishing of vision, seizures, macroencephaly due to cerebral gliosis, and the characteristic cherry-red spot in the retina. Affected individuals typically do not survive past age 5.
The juvenile or subacute form of Tay-Sachs disease often presents between 2 and 10 years with ataxia and clumsiness. Patients develop difficulties with speech and cognition. Neurologic features progressively worsen and death is typically 2 to 4 years later.
Disease progression is slower in patients with chronic or adult-onset Tay-Sachs disease. 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 (loss of speech), 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.
The carrier frequency of Tay-Sachs disease is increased in certain groups including individuals of Ashkenazi Jewish, Celtic, and French Canadian ancestry. A common cause of false-positive carrier screening by enzyme analysis, particularly among individuals of non-Ashkenazi Jewish descent, is due to the presence of a pseudodeficiency allele. Such sequence variations are not associated with disease, but result in the production of a hexosaminidase A enzyme with decreased activity towards the artificial substrate typically used in the enzyme assay. The recommended testing strategy is to order NAGR/82943 Hexosaminidase A and Total, Leukocytes/Molecular Reflex, which begins with enzyme analysis and when the percent of hexosaminidase A enzyme is low, reflexes to the molecular panel which includes the most common mutations observed in these high-risk populations and 2 common pseudodeficiency alleles.
Sandhoff Disease:
Sandhoff disease (deficiency of hexosaminidase A and B due to a defect in the beta subunit) is an autosomal recessive condition resulting from 2 mutations in the HEXB gene, which encodes for the beta subunit of hexosaminidase. Individuals with Sandhoff disease have deficiencies in both hexosaminidase A and hexosaminidase B. Phenotypically, patients with Sandhoff disease present with features very similar to Tay-Sachs disease including variability in age of onset and severity. Enzyme analysis is generally required to distinguish between the 2 disorders. Unlike Tay-Sachs disease, Sandhoff disease does not have an increased carrier frequency in any specific population.
Diagnostic and Carrier Testing:
Testing for Tay-Sachs and Sandhoff diseases occurs by analysis of hexosaminidase A, a heat-labile enzyme, and total hexosaminidase (hexosaminidase A plus hexosaminidase B). When testing the enzyme, an artificial substrate is most commonly used. The total hexosaminidase is quantified. Following this, heat inactivation of hexosaminidase A occurs with a second measurement of the total enzyme level. From this, the percent hexosaminidase A is calculated. Biochemically, Tay-Sachs disease is characterized by normal total hexosaminidase with a very low percent hexosaminidase A. Carriers of Tay-Sachs disease are asymptomatic, but have intermediate percent hexosaminidase A in serum, leukocytes, and cultured fibroblasts. Follow-up molecular testing is recommended for all individuals with enzyme results in the carrier or possible carrier ranges to differentiate carriers of a pseudodeficiency allele from those with a disease-causing mutation. In addition, this allows for the facilitation of prenatal diagnosis for at-risk pregnancies.
A very small group of patients affected with Tay-Sachs disease have the B1 variant. In the presence of an artificial substrate, the B1 variant allows for a heterodimer formation of hexosaminidase A and exhibits activity. However, in vivo the B1 variant hexosaminidase A is inactive on the natural substrate. Thus, with the artificial substrate, these patients appear to be unaffected. Individuals with the B1 variant of Tay-Sachs disease must be distinguished using a natural substrate assay (MUGS/80350 Hexosaminidase A (MUGS), Serum). This testing should be considered if one of the other assays indicates normal or carrier results and the suspicion of Tay-Sachs disease remains high.
Hexosaminidase testing using the artificial substrate provides an indirect assay for Sandhoff disease. Affected individuals exhibit very low total hexosaminidase with a disproportionately high percent hexosaminidase A due to alpha subunit homodimer formation. Carriers of Sandhoff disease are asymptomatic but have intermediate levels of total hexosaminidase with high percent hexosaminidase A in serum, leukocytes, and cultured fibroblasts. However, not all individuals with this pattern are true carriers of Sandhoff disease and follow-up molecular testing is recommended. In addition, molecular analysis allows for the facilitation of prenatal diagnosis for at-risk pregnancies. Testing hexosaminidase using the natural substrate does not identify homozygotes or heterozygotes for Sandhoff disease.
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, S
< or =15 years: > or =20 nmol/min/mL
> or =16 years: 10.4-23.8 nmol/min/mL
HEXOSAMINIDASE PERCENT A, S
< 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
This test cannot be performed on pregnant females.
GM2 activator deficiency (GM2-gangliosidosis, AB variant) is a rare disorder with clinical features similar to Tay-Sachs and Sandhoff diseases; however, levels of both hexosamindase A and B are normal. GM2 activator deficiency cannot be identified through testing offered at Mayo Medical Laboratories.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Gravel RA, Kaback MM, Proia RL, et al: The GM2 gangliosidosis. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, available from URL: www.ommbid.com. Accessed 11/6/12
2. Maegawa G, Stockley T, Tropac M, et al: The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported. Pediatrics 2006 Nov;118(5):e1550-1562
3. 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;283:15-20
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 two 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 on a two channel Autoanalyzer equipped with two fluorometers. 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.
After sample pickup, a sample splitter divides the patient serum. One-half of the sample travels through a 37 degree C mixing coil with substrate. The other half is first directed through a 53.25 degree C heating coil for 5.5 minutes and is then mixed with substrate and sent through the 37 degree C mixing coil. 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 reactants are pumped through a fluorometer, and the intensity of the fluorescence is converted to peaks of varying heights on a recorder. Sample peaks are compared to that of a 100 microM beta-methylumbelliferone standard 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: Lysosomal storage diseases. In Tietz Textbook of Clinical Chemistry. Edited by CA Burtis, ER Ashwood. Second edition. Philadelphia, PA, WB Saunders Company, 1994. pp 2149-2160)
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.
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.
83080
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 |
|---|---|---|
| 27612 | Hexosaminidase Total, S | 1956-2 |
| 27613 | Hexosaminidase Percent A, S | 12914-8 |
| 27216 | Interpretation (NAGS) | 59462-2 |
| 27218 | Reviewed By | N/A |
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