Clinical Information

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 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: GAG). Accumulation of MPS in lysosomes interferes with normal functioning of cells, tissues, and organs.

Clinical features and severity of symptoms of MPS IVA are widely variable and affect multiple body systems. Clinical features may include skeletal dysplasia, 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 levels of urinary MPS and increased keratan sulfate and chondroitin-6-sulfate detected via quantitative and qualitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the specific sulfates. 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 is necessary to distinguish between the 2 types. Reduced or absent activity of N-acetylgalactosamine-6-sulfate sulfatase enzyme in leukocytes and/or fibroblasts can confirm a diagnosis of MPS IVA. Sequencing of the GALNS gene allows for detection of disease-causing variants in affected patients and identification of familial variants allows for testing of at-risk family members.