Sorted By Test Name - Mayo Medical Laboratories

ARSAS
61259
ARSAK
number variation and new reports classifying specific copy number variation as pathogenic or benign
enter the literature frequently, thus the interpretation of any given copy number variation may evolve
rapidly as more information becomes available. It is recommended that a qualified professional in
Medical Genetics communicate all abnormal results to the patient.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Miller DT, Adam MP, Aradhya S, et al: Consensus statement:
Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental
disabilities or congenital anomalies. Am J Hum Genet 2010; 86:749-764 2. Manning M, Hudgins L:
Professional Practice and Guidelines Committee: Array-based technology and recommendations for
utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med
2010;12(11):742-745
ARSA Gene, Full Gene Analysis
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: ARST/8778 Arylsulfatase A, Leukocytes and ARSU/8777 Arylsulfatase A, 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.
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
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 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
ARSA Gene, Known Mutation
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