Arylsulfatase A, Fibroblasts
Detection of metachromatic leukodystrophy
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
First order ARSAW/8779 Arylsulfatase A, Leukocytes and ARSU/8777 Arylsulfatase A, Urine.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by a deficiency of the arylsulfatase A enzyme, which leads to the accumulation of galactosyl sulfatide (cerebroside sulfate) in the white matter of the central nervous system and in the peripheral nervous system. 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.
The 3 clinical forms of MLD are late-infantile, juvenile, and adult, depending on age of onset. All result in progressive neurologic changes and leukodystrophy demonstrated on magnetic resonance imaging. Late-infantile MLD is the most common (50%-60% of cases) and typically presents between 1 to 2 years of age with hypotonia, clumsiness, diminished reflexes, and slurred speech. Progressive neurodegeneration occurs with a typical disease course of 3 to 10 years. Juvenile MLD (20%-30% of cases) is characterized by onset between 4 to 14 years. Typical presenting features are behavior problems, declining school performance, clumsiness, and slurred speech. Neurodegeneration occurs at a somewhat slower and more variable rate than the late-infantile form. Adult MLD (15%-20% of cases) has an onset after puberty and can be as late as the fourth or fifth decade. Presenting features are often behavior and personality changes, including psychiatric symptoms; clumsiness, neurologic symptoms, and seizures are also common. The disease course has variable progression and may occur over 2 to 3 decades. The disease prevalence is estimated to be approximately 1 in 100,000.
MLD is an autosomal recessive disorder and is caused by mutations in the ARSA gene coding for the arylsulfatase A enzyme. This disorder is distinct from conditions caused by deficiencies of arylsulfatase B (Maroteaux-Lamy disease) and arylsulfatase C (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. 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.
Current treatment options for MLD are usually focused on managing disease manifestations such as seizures. Bone marrow transplantation remains controversial, and the effectiveness of enzyme replacement therapy may be limited due to difficulties crossing the blood-brain barrier. Other treatments under ongoing investigation include hematopoietic stem cell transplantation and fetal umbilical cord blood transplantation.
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.
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.
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.
Depression of arylsulfatase activity does not clearly indicate metachromatic leukodystrophy. The pseudogene could be present resulting in lowered activity. Arylsulfatase A is also deficient in individuals with multiple 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).
Clinical Reference 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, The McGraw-Hill Companies, Inc. Available from URL: ttp://www.ommbid.com/OMMBID/a/c.html/lysosomal_disorders/metachromatic_leukodystrophy/abstract
2. Fluharty AL: Arylsulfatase A Deficiency. Available from URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=krabbe Reviewed September 23, 2008