Clinical Information

Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by the deficiency of N-acetylgalactosamine 4-sulfatase, also known as arylsulfatase B (ARSB) leading to the accumulation of dermatan sulfate. Clinical features and severity of symptoms are widely variable, but typically include short stature, dysostosis multiplex, and degenerative joint disease. Other clinical features may include facial dysmorphism, 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. Treatment options include hematopoietic stem cell transplantation and/or enzyme replacement therapy.

The differential diagnosis of ARSB deficiency should include multiple sulfatase deficiency and mucolipidosis II (I-Cell disease), however both 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 (ARSAW/ Arylsulfatase A, Leukocytes) 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 (NAGS/ Hexosaminidase A and Total Hexosaminidase, Serum) is recommended if a diagnosis of I-cell is suspected.

A diagnostic workup for MPS includes glycosaminoglycan (GAG) determination in urine (MPSQU / Mucopolysaccharides Quantitative, Random, Urine) or blood (MPSBS / Mucopolysaccharidosis, Blood Spot, or MPSER / Mucopolysaccharidosis, Serum) and molecular genetic analysis of the relevant gene. For MPS VI, molecular analysis of the ARSB gene (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify Gene List ID: IEMCP-QQF7DP) allows for detection of disease-causing variant in affected patients and subsequent carrier detection in relatives.