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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 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
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name
ARSA Gene, Full Gene AnalysisSpecimen Type
VariesForms:
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
3. If not ordering electronically, complete, print, and send a Neurology Test Request Form-General (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)
Specimen preferred to 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 [T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen Type: Blood spot
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
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.
Cautions
A small percentage of individuals who are carriers or have a diagnosis of metachromatic leukodystrophy (MLD) may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of MLD. The preferred approach to carrier testing is to first document the presence of an ARSA gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
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.
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.
Day(s) Performed
Performed weekly; Varies
Report Available
14 daysPerforming Laboratory
Mayo Medical Laboratories in Rochester
Test 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)