Epic Test Code LAB2561 Hexosaminidase A and Total Hexosaminidase, Leukocytes
Additional Codes
MML Code: NAGW
LIS Code: TAYL
NY State Approved
YesPerforming Laboratory
Mayo Clinic Laboratories in RochesterReporting Name
Hexosaminidase A and Total, WBCMethod Name
Heat Inactivation, Fluorometric, Semi-Automated
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Whole Blood ACD | Refrigerated (preferred) | 6 days | YELLOW TOP/ACD |
Ambient | 6 days | YELLOW TOP/ACD |
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):
-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
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.
Specimen Type
Whole Blood ACDSpecimen Minimum Volume
5 mL
Reference Values
Hexosaminidase total
≤15 years: ≥20 nmol/min/mg
≥16 years: 16.4-36.2 nmol/min/mg
Hexosaminidase percent A
≤15 years: 20-80% of total
≥16 years: 63-75% of total
Report Available
2 to 8 daysDay(s) Performed
Preanalytical processing: Monday through Saturday
Assay performed: FridayCPT Code Information
83080 x 2
Reject Due To
Gross hemolysis | Reject |
Useful For
Carrier detection and diagnosis of Tay-Sachs disease
Carrier detection and diagnosis of Sandhoff disease
Testing Algorithm
For more information see Tay-Sachs and Related Disorders Diagnostic Testing Algorithm
Special Instructions
Clinical Information
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.
Interpretation
Interpretation is provided with report.
Cautions
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.
Specimen Retention Time
White blood cell homogenate: 1 monthForms
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.