Test ID: TSD
Tay-Sachs Disease, Mutation Analysis, HEXA
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
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 testing of individuals of Ashkenazi Jewish ancestry or who have a family history of Tay-Sachs disease
Determining carrier status for individuals with enzyme activity within the carrier or equivocal ranges
Prenatal diagnosis for at-risk families
Confirmation of suspected clinical diagnosis of Tay-Sachs disease in individuals of Ashkenazi Jewish ancestry
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Familial mutations and carrier screen results must be known prior to prenatal testing. Mutations and alterations tested for include 1278insTATC, IVS9(+1)G>A, IVS12(+1)G>C, G269S, delta7.6kb, R247W (pseudodeficiency allele), and R249W (pseudodeficiency allele).
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| FBC | Fibroblast Culture for Genetic Test | Yes | No |
| AFC | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
For prenatal specimens only: If amniotic fluid (non-confluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (non-confluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.
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
Polymerase chain reaction (PCR) analysis is used to test for the following mutations associated with Tay-Sachs disease: 1278insTATC, G269S, IVS12(+1)G->C, IVS9(+1) G->A, delta 7.6kb, R247W, R249W.
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
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
GM2 Gangliosidosis
Hexosaminidase A
Hexosaminidase A Deficiency
Tay-Sachs Disease (TSD)
TSD (Tay-Sachs Disease)
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.
Forms:
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. Molecular Genetics-Biochemical Disorders Patient Information Sheet (Supply T527) in Special Instructions
Specimen must arrive within 96 hours of collection.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 2.6 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient (preferred)/Refrigerated/Frozen
Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MCC/88636 Maternal Cell Contamination, Molecular Analysis on the maternal specimen.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20 mg
Specimen Stability Information: Refrigerated
Acceptable:
Specimen Type: Confluent cultured cells
Container/Tube: T-25 flask
Specimen Volume: 2 flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred)/Refrigerated
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 | NA |
| Lipemia | NA |
| 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 |
|---|---|---|
| Varies | Varies | |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Tay-Sachs disease is caused by an absence of hexosaminidase (Hex A) enzyme activity, which results in the accumulation of the sphingolipid GM2 ganglioside. Mutations within the alpha subunit of the hexosaminidase A gene, HEXA, cause the clinical manifestations associated with Tay-Sachs disease (TSD). The classic form of TSD becomes apparent in infancy when mild motor weakness is noted along with impaired visual acuity and the presence of a "startle response." Other manifestations of this condition include progressive neurodegeneration, seizures, and blindness leading to total incapacitation and death. Other types of TSD (eg, subacute and adult onset) are characterized by later ages of onset and death. The symptoms and severity of disease vary widely.
TSD is inherited in an autosomal recessive manner. The carrier frequency for TSD disease in the Ashkenazi Jewish population is 1/31. This panel tests for the 3 common mutations in the Ashkenazi Jewish population: 1278insTATC, G269S, and IVS12+1G->C. When performed in conjunction with hexosaminidase A biochemical testing, the mutation detection rate using this assay is approximately 99%. Also included in this analysis are the mutations IVS9+1G->A and 7.6 kbdel 5'UTR-IVS+1 that are over-represented in individuals of Celtic or French Canadian ancestry, respectively.
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, either R247W or R249W. These sequence variations are not associated with disease, but result in the production of a hexosaminidase A enzyme with decreased activity towards the artificial substrate used in the enzyme assay. Both pseudodeficiency alleles are evaluated for by this panel.
The recommended first-tier test to screen for TSD is biochemical analysis measuring hexosaminidase enzyme activity, NAGW/8775 Hexosaminidase A and Total Hexosaminidase, Leukocytes. Molecular tests form the basis of confirmatory diagnostic or carrier testing. See Tay-Sachs Disease Carrier Testing Protocol in Special Instructions for additional information. Refer to Carrier Testing for Tay-Sachs Disease and Other GM2 Gangliosidosis Variants: Supplementing Traditional Biochemical Testing with Molecular Methods, Mayo Medical Laboratories Communique 2004 Jul;29(7) for more information regarding diagnostic strategy.
Alternatively, full gene sequencing is available to evaluate for mutations in all coding regions and exon/intron boundaries of the HEXA gene by ordering HEXMS/89278 Tay-Sachs Disease, HEXA Gene, Full Gene Analysis.
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.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the mutations that cause Tay-Sachs disease. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
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. Eigth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, available at www.ommbid.com Accessed 3-18-10
2. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening individuals of Ashkenazi Jewish descent. Genet Med 2008;10(1):54-56
Method Description Describes how the test is performed and provides a method-specific reference
A laboratory-developed multiplex PCR-based assay is used to detect the following mutations in the HEXA gene: 7.6kb, R247W, R249W, G269S, IVS9+1G->A, 1278insTATC, and IVS12+1G->C.(Fulton R, McDade R, Smith P, et al: Advanced multiplexed analysis with the FlowMetrix system. Clin Chem 1997;43:1749-1756; Ye F, Li MS, Taylor JD, et al: Fluorescent microsphere-based readout technology for multiplexed human single nucleotide polymorphism analysis and bacterial identification. Hum Mutat 2001 Apr;17[4]:305-316)
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 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.
81255-HEXA (hexosaminidase A, alpha polypeptide) (eg, Tay-Sachs disease) gene analysis, common variants (eg, 1278insTATC, 1421+1G->C, G269S)
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 |
|---|---|---|
| 17379 | Specimen | 31208-2 |
| 17380 | Specimen ID | N/A |
| 17381 | Source | N/A |
| 17382 | Order Date | N/A |
| 17383 | Reason For Referral | 42349-1 |
| 17384 | Method | In Process |
| 17385 | Result | 32632-2 |
| 17386 | Interpretation | 69047-9 |
| 17387 | Amendment | In Process |
| 17388 | Reviewed By: | N/A |
| 17389 | Release Date | N/A |
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