Clinical Information

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 (referred to as mucopolysaccharides [MPS] or glycosaminoglycans). Accumulation of MPS in lysosomes interferes with normal functioning of cells, tissues, and organs.

Mucopolysaccharidosis IVA, (MPS IVA; Morquio A syndrome) is an autosomal recessive mucopolysaccharidosis caused by reduced or absent N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme activity. The glycosaminoglycans, keratan and chondroitin sulfate, accumulate in multiple tissues but mainly bone, cartilage, heart valves, and cornea.  Clinical features and severity of symptoms of MPS IVA are widely variable affecting multiple body systems, in particular the skeletal system. Other clinical features may include short stature, dental anomalies, corneal clouding, respiratory insufficiency, and cardiac disease. Intelligence is usually normal. Treatment options are mostly limited to symptom management; however, more recently available enzyme replacement therapy has shown to be effective in improving some function and quality of life for individuals with MPS IVA. Estimates of the incidence of MPS IVA syndrome range from 1 in 200,000 to 1 in 300,000 live births.

A diagnostic workup in an individual with MPS IVA typically demonstrates elevated urinary levels of keratan sulfate and chondroitin-6-sulfate. Reduced or absent activity of N-acetylgalactosamine-6-sulfate sulfatase enzyme in leukocytes and/or fibroblasts can confirm the diagnosis. Sequencing of the GALNS gene (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify Gene List ID: EMCP-JUFPRX) allows for detection of disease-causing variants in affected patients and identification of familial variants allows for testing of at-risk family members. Morquio B is a distinct disorder caused by a deficiency of beta-galactosidase and has a significant number of overlapping clinical features with MPS IVA. Enzyme analysis (BGAW / Beta-Galactosidase, Blood) is necessary to distinguish between the 2 types.