Arylsulfatase A, Fibroblasts
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 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 (ARSAS / ARSA Gene, Full Gene Analysis), urinary excretion of sulfatides (CTSA / 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.
Detection of metachromatic leukodystrophy
Arylsulfatase A is deficient in metachromatic leukodystrophy and multiple sulfatase deficiency.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not suitable for carrier status detection due to both analytical and unusual genetic variation. Individuals with pseudodeficiency of arylsulfatase A may have decreased enzyme activity and are not clinically affected with metachromatic leukodystrophy.
Arylsulfatase A is also deficient in individuals with multiple sulfatase deficiency.
This disorder is distinct from conditions caused by deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (steroid sulfatase deficiency).
Interfering factors include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, and exposure of the specimen to temperature extremes (freezing or >30 degrees C).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =4.25 nmol/min/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Jaeken J, Gieselmann V, von Figura K: Metachromatic leukodystrophy. In Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMMBID). Edited by D Valle, et al. McGraw-Hill Companies, Inc. Available from URL: http://www.ommbid.com/OMMBID/a/c.html/lysosomal_disorders/metachromatic_leukodystrophy/abstract
2. Fluharty AL: Arylsulfatase A Deficiency. In GeneReviews. Edited by RA Pagon, TD Bird, CR Dolan, et al: Seattle (WA): University of Washington, Seattle, 1993. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1130/
3. Mahmood A, Berry J, Wenger D, et al: Metachromatic leukodystrophy: a case of triplets with the late infantile variant and a systematic review of the literature. J Child Neurol 2010;25(5):572-580