Test ID: ARSAK
ARSA Gene, Known Mutation
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 with a family history of metachromatic leukodystrophy (MLD)
Diagnostic confirmation of MLD when familial mutations have been previously identified
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Documentation of the specific familial mutation must be provided with the specimen in order to perform this test.
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.
If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.
For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent 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.
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) Followed by DNA Sequence Analysis
(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
Leukodystrophy
MLD
Arylsulfatase A Deficiency
Arylsulfatase A
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:
Preferred:
Specimen Type: Blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient (preferred)/Refrigerated/Frozen
Specimen Type: Cultured fibroblasts
Container/Tube: T-75 or T-25 flask
Specimen Volume: 1 full T-75 or 2 full T-25 flasks
Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours
Specimen Type: Skin biopsy
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [Supply T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Acceptable:
Specimen Type: Blood spot
Container/Tube: Whatman Protein Saver 903 Paper
Specimen Volume: 5 blood spots
Collection Instructions:
1. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.
2. Do not expose specimen to heat or direct sunlight.
3. Do not stack wet specimens.
4. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
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
Metachromatic leukodystrophy (MLD) is a rare autosomal recessive condition caused by mutations in the arylsulfatase A gene (ARSA). The incidence of MLD is approximately 1:40,000 to 1:160,000, and the estimated carrier frequency in the general population is 1:100 to 1:200. MLD is characterized by the accumulation of cerebroside sulfate, which causes progressive demyelination and the loss of white matter.
There is a variable age of onset. In the early onset form, symptoms appear in the first 1 to 2 years of life and include deterioration of skills such as walking and speaking. In the juvenile form, symptoms can appear between 4 years of age and the age of sexual maturity, and can include a decline in school performance and behavioral problems. Adults can present with a decline in school or job performance, substance abuse, and emotional lability. The diagnosis is suspected in individuals with progressive neurologic dysfunction and molecular resonance imaging evidence of leukodystrophy.
The ARSA gene is located on chromosome 22 and has 8 exons. The following 4 mutations, c.459+1G>A, c.1204+1G>A, p.Pro426Leu, and p.Ile179Ser, account for 25% to 50% of mutations in the central and western European populations.
The recommended first-tier tests to screen for MLD are biochemical tests that measure arylsulfatase A enzyme activity in leukocytes and urine ARST/8778 Arylsulfatase A, Leukocytes and ARSU/8777 Arylsulfatase A, Urine. However, arylsulfatase A enzyme assays cannot distinguish between MLD and ARSA pseudodeficiency, a clinically benign condition that leads to low in vitro ARSA levels, but it is found in 5% to 20% of the normal population. Thus, the diagnosis of MLD must be confirmed by molecular analysis of the ARSA gene.
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
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order ARSAS/61259 ARSA Gene, Full Gene Analysis.
Analysis is performed only for the provided familial mutations. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic 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.
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. Biffi A, Cesani M, Fumagalli F, et al: Metachromatic leukodystrophy-mutation analysis provides further evidence of genotype-phenotype correlation. Clin Genet 2008 Oct;74(4):349-357
2. Gieselmann V, Krageloh-Mann I: Metachromatic leukodystrophy-an update. Neuropediatrics 2010 Feb;41(1):1-6, Epub 2010 Jun 22
3. Kreysing J, von Figura K, Gieselmann V: Structure of the arylsulfatase A gene. Eur J Biochem 1990 Aug 17;191(3):627-631
4. Polten A, Fluharty AL, Fluharty CB, et al: Molecular basis of different forms of metachromatic leukodystrophy. N Engl J Med 1991 Jan 3;324(1):18-22
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequencing is utilized to test for the presence of specific mutations in the ARSA gene that were previously identified in an affected family member.(Unpublished Mayo method)
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.
Monday, 10 am
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.
81479-Unlisted molecular pathology procedure
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 |
|---|---|---|
| 33327 | Specimen | N/A |
| 33328 | Specimen ID | N/A |
| 33329 | Source | N/A |
| 33330 | Order Date | N/A |
| 33331 | Reason For Referral | N/A |
| 33332 | Method | N/A |
| 33333 | Result | N/A |
| 33334 | Interpretation | N/A |
| 33335 | Amendment | N/A |
| 33336 | Reviewed By | N/A |
| 33337 | Release Date | N/A |
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