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HelpTest ID: ARSAZ ARSA Gene, Full Gene Analysis
Useful For
Second-tier test for confirming a diagnosis of metachromatic leukodystrophy (MLD) based on clinical findings and low arylsulfatase A (ARSA) activity levels
Carrier testing when there is a family history of MLD, but disease-causing mutations have not been previously identified
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
Reporting Name
ARSA Gene, Full Gene AnalysisSpecimen Type
VariesShipping Instructions
Specimen preferred to arrive within 96 hours of draw.
Specimen Required
Patient Preparation: 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.
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 [T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen Type: Blood spot
Supplies: Card - Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card (T493)
Specimen Volume: 2 to 5 Blood Spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card, T493)
Collection Instructions:
1. An alternative blood collection option for a patient >1 year of age is finger stick.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.
2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.
Specimen Minimum Volume
Blood: 1 mL
Blood Spots: 5 punches-3 mm diameter
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Clinical Information
Metachromatic leukodystrophy (MLD) is a rare autosomal recessive condition caused by mutations in the arylsulfatase A (ARSA) gene. 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 presence of 2 of these mutations within the ARSA gene confirms a diagnosis of metachromatic leukodystrophy.
The recommended first-tier tests to screen for MLD are biochemical tests that measure arylsulfatase A enzyme activity in leukocytes and urine: ARSAW / Arylsulfatase A, Leukocytes and ARSU / Arylsulfatase A, 24 Hour, Urine. Individuals with decreased enzyme activity are more likely to have 2 mutations in the ARSA gene identifiable by molecular gene testing. 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
An interpretive report will be provided.
Interpretation
All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424
2. 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
3. Gieselmann V, Krageloh-Mann I: Metachromatic leukodystrophy-an update. Neuropediatrics 2010 Feb;41(1):1-6, Epub 2010 Jun 22
4. Kreysing J, von Figura K, Gieselmann V: Structure of the arylsulfatase A gene. Eur J Biochem 1990 Aug 17;191(3):627-631
5. 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
Day(s) and Time(s) Performed
Performed weekly; Varies
Analytic Time
14 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
81405 ARSA (arylsulfatase A) (eg, arylsulfatase A deficiency), full gene sequence
Fibroblast Culture for Genetic Test
88233-Tissue culture, skin or solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| ARSAZ | ARSA Gene, Full Gene Analysis | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 53456 | Result Summary | 50397-9 |
| 53457 | Result | In Process |
| 53458 | Interpretation | 69047-9 |
| 53459 | Additional Information | 48767-8 |
| 53460 | Specimen | 31208-2 |
| 53461 | Source | 31208-2 |
| 53462 | Released By | 18771-6 |
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 (T576) is available in Special Instructions.
2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions
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