Test ID: ARST
Arylsulfatase A, Fibroblasts

Detection of metachromatic leukodystrophy

First order ARSAW/8779 Arylsulfatase A, Leukocytes and ARSU/8777 Arylsulfatase A, Urine.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder of myelin metabolism. It is 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, PNS, and many organs, and can be identified in stained frozen tissue sections. MLD results from decreased arylsulfatase A activity and can be classified according to age of onset and severity. Late infantile, juvenile, and adult forms of the disease have been described. Clinical features typically include psychomotor regression with gradual worsening of cortical cerebellar and peripheral nerve function, speech and feeding difficulties, optic atrophy, and in adult cases, psychiatric symptoms. Although not without significant risk, bone marrow transplant is the only treatment known to affect the progression of MLD.

There are 3 forms of arylsulfatase: A, B, and C. Arylsulfatase A (ARSA) is associated with hydrolysis of galactosyl sulfatide (metachromatic leukodystrophy). 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 patients and patients with multiple sulfatase deficiency (MSD); therefore, assay of enzymatic activity alone cannot distinguish between true MLD patients and those with low enzyme activity attributed to either "pseudodeficiency" or MSD. Additional studies, such as molecular genetic testing of ARSA, urinary excretion of sulfatides (CTSA/81979 Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, Urine) and/or histological analysis for metachromatic lipid deposits in nervous system tissue are recommended to confirm a diagnosis.

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

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

2.28-15.74 U/g of cellular protein

In metachromatic leukodystrophy (MLD), the activity of serum arylsulfatase A is greatly reduced. Values expected in MLD are <1.5 U/g of cellular protein.

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

Depression of arylsulfatase activity does not clearly indicate MLD. The pseudogene could also be present resulting in lowered activity.

Interfering factors:

-Lack of viable cells or bacterial contamination

-Failure to transport tissue in appropriate media

-Excessive transport time

-Exposure of the specimen to temperature extremes (freezing or >30 degrees C)

1. Jaeken J, Gieselmann V, von Figura K: Metachromatic Leukodystrophy. In Scriver’s The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID) Edited by Valle D, et al, The McGraw-Hill Companies, Inc.

2. Fluharty AL: Arylsulfatase A Deficiency. Available from http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=krabbe Reviewed September 23, 2008

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