Clinical Information

The mucopolysaccharidoses (MPS) are a group of disorders caused by a deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate also known as glycosaminoglycans (GAG). Accumulation of GAG in lysosomes interferes with normal functioning of cells, tissues, and organs. There are 11 known disorders that involve the accumulation of GAG which affects multiple organ systems. These disorders have a broad clinical spectrum and can present with coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature, and skeletal abnormalities. This assay detects 8 of the 11 known MPS, including MPSII, MPSIIIA, MPSIIIB, MPSIIIC, MPSIVA, MPSIVB, MPSVI, and MPSVII.

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive lysosomal disorder caused by mutations in the sulfatase-modifying factor 1 (SUMF1) gene. SUMF1 encodes for a formylglycine-generating enzyme that performs a critical posttranslational modification necessary for activation of all human sulfatases, including arylsulfatase A and B. The clinical features of MSD resemble symptoms of every single sulfatase deficiency, including metachromatic leukodystrophy, the mucopolysaccharidoses, X-linked ichthyosis, and chondrodysplasia punctata type I. Age of onset and clinical severity are variable and correspond with the level of residual enzyme activity. Individuals with MSD typically demonstrate reduced activity of several sulfatase enzymes including those on this panel (iduronate-2-sulfatase, heparan sulfate sulfatase, galactosamine-6-sulfate sulfatase, and arylsulfatase B).

Mucolipidosis II (MLII), also known as I-cell disease, is a rare autosomal recessive disorder with features of both mucopolysaccharidoses and sphingolipidoses. I-cell disease is a progressive disorder characterized by congenital or early infantile manifestations including coarse facial features, short stature, skeletal anomalies, cardio- and hepatomegaly, and developmental delays. While not intended for I-cell disease, a pattern of reduced activity of several enzymes and increased activity of others may indicate MLII.