Test ID: ARSAW
Arylsulfatase A, Leukocytes

Preferred test to rule-out metachromatic leukodystrophy.

Preferred test to rule-out metachromatic leukodystrophy. Not

reliable in identifying carriers due both to analytical variation

and unusual genetic variants. The urine assay should be used

to confirm leukocyte results.

Metachromatic leukodystrophy (MLD) is an inherited disorder of myelin metabolism characterized by accumulation of galactosyl sulfatide (cerebroside sulfate) in the white matter of the central nervous system (CNS) and in the peripheral nervous system (PNS). Galactosyl sulfatide and, to a smaller extent, lactosyl sulfatide, also accumulate within the kidney, gallbladder, and other visceral organs and are excreted in excessive amounts in the urine. Metachromatic granules are deposited in the CNS and PNS and many organs, and can be identified in stained frozen tissue sections. MLD is the result of decreased arylsulfatase A activity. The mode of inheritance is autosomal recessive. The human arylsulfatase A gene has been mapped to chromosome 22, several polymorphisms defined, and a number of disease-related mutations identified.

There are 3 forms of arylsulfatase: A, B, and C. Arylsulfatase A is associated with hydrolysis of galactosyl sulfatide. Arylsulfatase B is associated with mucopolysaccharide metabolism (Maroteaux-Lamy disease). Arylsulfatase C is a major component of myelin sheaths and is associated with X-linked icthyosis (steroid sulfatase deficiency).

Extremely low arylsulfatase A levels have been found in some clinically normal parents and other relatives of MLD patients. These individuals do not have metachromatic deposits in peripheral nerve tissues, and their urine content of sulfatide is normal. Individuals with this "pseudodeficiency" have been recognized with increasing frequency among patients with other apparently unrelated neurologic conditions as well as among the general population. This has been associated with a fairly common polymorphism in the arylsulfatase A gene which leads to low expression of the enzyme (5%-20% of normal). These patients can be difficult to differentiate from actual MLD patients.

This test is not suitable for carrier status detection due to both analytical and unusual genetic variation.

Treatment options for MLD are few. Bone marrow transplantation appears to slow the progression of symptoms, but benefits are not seen for several months. Other promising research includes protease inhibitor treatments, enzyme replacement, and gene replacement therapies.

See Lysosomal Storage Disorders in Special Instructions for further information on lysosomal storage disease.

> or =62 nmol/h/mg

Note: Results from this assay may not reflect carrier status because of individual variation of arylsulfatase A enzyme levels. Low normal values may be due to the presence of pseudodeficiency gene or carrier gene. Patients with these depressed levels may be phenotypically normal.

Detection of metachromatic leukodystrophy (MLD). Carriers or persons with a pseudogene may yield low results but are unaffected with MLD.

Abnormal results should be confirmed using #8777 Arylsulfatase A, Urine.

This test is not reliable in identifying carriers due both to analytical variation and unusual genetic variants.

Due to the use of artificial substrate, this test does not reliably pick up carriers.

von Figura K, Gieselmann V, Jacken J: Metachromatic leukodystrophy. In The Metabolic and Molecular Basis of Inherited Disease. Vol. 3. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company, 2001, pp 3695-3716

• Lysosomal Storage Disorders
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