Arylsulfatase B, Fibroblasts
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine 4-sulfatase, also known as arylsulfatase B (ARSB). The mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of complex macromolecules called glycosaminoglycans (GAGs) including dermatan sulfate, heparan sulfate, keratan sulfate, and chondroitin sulfate. Accumulation of GAGs (also called mucopolysaccharides) in lysosomes interferes with normal functioning of cells, tissues, and organs. MPS VI is caused by a reduced or absent activity of the ARSB enzyme and gives rise to the physical manifestations of the disease.
Clinical features and severity of symptoms are widely variable, but typically include short stature, dysostosis multiplex, facial dysmorphism, stiff joints, hepatosplenomegaly, corneal clouding, and/or cardiac defects. Intelligence is usually normal. Rapidly progressing forms have an early onset of symptoms, significantly elevated GAGs, and can lead to death before the second or third decades. A more slowly progressing form has a later onset, milder skeletal manifestations, smaller elevations of GAGs, and typically a longer lifespan. Estimates of the incidence of MPS VI range from 1 in 250,000 to 1 in 300,000. Treatment options include hematopoietic stem cell transplantation and/or enzyme replacement therapy.
A diagnostic workup in an individual with MPS VI typically demonstrates elevated levels of urinary GAGs and increased dermatan sulfate detected on thin-layer chromatography. Reduced or absent activity of ARSB in leukocytes and/or fibroblasts indicates a diagnosis of MPS VI. Sequencing of the ARSB gene allows for detection of disease-causing mutations in affected patients and identification of familial mutations allows for testing of at-risk family members. Currently, no clear genotype-phenotype correlations have been established.
ARSB activity is also reduced in the rare autosomal recessive disorder multiple sulfatase deficiency (MSD), which is caused by abnormal posttranslational modification of a class of sulfatase enzymes. This defect causes a deficiency of 12 sulfatase enzymes, including those related to Sanfilippo syndrome types A and D, Hunter syndrome, Morquio syndrome type A, metachromatic leukodystrophy (MLD), and MPS VI. Clinical features can include developmental delay, neurologic regression, dysmorphic facies, dysostosis multiplex, organomegaly, ichthyosis, and chondroplasia punctata. If MSD is suspected, testing of an additional sulfatase enzyme (such as arylsulfatase A in MLD) can help determine if multiple sulfatases are deficient.
Diagnosis of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)
Arylsulfatase B is deficient in mucopolysaccharidosis VI 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 recommended for carrier testing for mucopolysaccharidosis VI (MPS VI).
The disorder multiple sulfatase deficiency may have reduced levels of arylsulfatase B, however the enzyme activity may not be as significantly decreased as in MPS VI. In addition, the clinical presentation between the 2 conditions is quite different.
Interfering factors in diagnosing MPS VI or multiple sulfatase deficiency include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, or 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 =6.08 nmol/min/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Valayannopoulos V, Nicely H, Harmatz P, Turbeville S: Mucopolysaccharidosis VI. Orphanet J Rare Dis. 2010 Apr 12;5:5
2. Neufeld EF, Muenzer J: The Mucopolysaccharidoses: In The Metabolic Basis of Inherited Disease. Seventh edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill 1995, pp 2465-2494
3. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 733-735