Interpretive Handbook

Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine 4-sulfatase (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 dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans, [GAGs]). Undegraded or partially degraded GAGs (also called mucopolysaccharides) are stored in lysosomes and/or are excreted in urine. Accumulation of GAGs (previously 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. 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.

Diagnosis of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Deficiency of arylsulfatase B is diagnostic of mucopolysaccharidosis VI.

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, but the enzyme activity is not as significantly decreased as in MPS type VI. In addition, the clinical presentation between the two conditions is quite different.

Interfering factors in diagnosing 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).

1.6-14.9 U/g of cellular protein

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. 7th 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