Clinical Information

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.

Clinical features and severity of symptoms are widely variable, but typically include short stature, dysostosis multiplex, facial dysmorphism, stiff joints, hepatosplenomegaly, corneal clouding, and cardiac disease. 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 is suggestive of 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 (MPS6Z / Mucopolysaccharidosis VI, Full Gene Analysis). Currently, no clear genotype-phenotype correlations have been established.

ARSB activity is also reduced in 2 other rare autosomal recessive disorders, multiple sulfatase deficiency (MSD) and mucolipidosis II (I-cell disease). Both of these conditions present with developmental delays that make them clinically different from MPS VI. The symptoms of MSD mimic metachromatic leukodystrophy (MLD) as well as the mucopolysaccharidoses and 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. I-cell disease is characterized by congenital or early infantile manifestations including coarse facial features, short stature, skeletal anomalies, cardio- and hepatomegaly, and developmental delays. This is a progressive disorder and death typically occurs in the first decade of life. Additional testing including hydrolase enzymes in serum, such as hexosaminidase A in Tay-Sach disease, is recommended if a diagnosis of I-cell is suspected.