N-Acetylgalactosamine-6-Sulfate Sulfatase, Fibroblasts
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Mucopolysaccharidosis IVA, (MPS IVA, Morquio A syndrome) is an autosomal recessive lysosomal storage disorder 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 (glycosaminoglycans, GAGs). Accumulation of GAGs (previously called mucopolysaccharides) in lysosomes interferes with normal functioning of cells, tissues, and organs.
Clinical features and severity of symptoms of MPS IVA are widely variable, but may include skeletal dysplasia, short stature, dental anomalies, corneal clouding, respiratory insufficiency, and cardiac disease. Intelligence is usually normal. Estimates of the incidence of Morquio A 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 GAGs and increased keratan sulfate and chondroitin-6-sulfate detected on thin-layer chromatography. Morquio B is a genetically distinct disorder caused by a deficiency of beta-galactosidase and has a significant number of overlapping clinical features with Morquio A. 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 mutations in affected patients and identification of familial mutations allows for testing of at-risk family members.
Assisting in the diagnosis of Morquio A disease
Very low enzyme levels are consistent with Morquio A disease.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The test cannot be used to establish carrier status for Morquio A disease.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =163 nmol/17 hour/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Giugliani R, Harmatz P, Wraith JE: Management Guidelines for Mucopolysaccharidosis VI. Pediatrics 2007;120:405-418
2. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 732