Assisting in the diagnosis of Morquio A disease
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Preferred test to rule out Mucopolysaccharidosis IVA, (MPS IVA, Morquio A syndrome). Not recommended for carrier detection.
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 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 (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 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 Morquio A. 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 via quantitative and qualitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the specific sulfates. 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.
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 =92 nmol/17 hour/mg protein
Very low enzyme activity 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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Hendriksz CJ, Harmatz P, Beck M, et al: Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab 2013 Sep-Oct;110(1-2):54-64. DOI: 10.1016/j.ymgme.2013.04.002
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
3. Haddley K: Elosulfase alfa. Drugs Today (Barc) 2014 Jul;50(7):475-483. DOI: 10.1358/dot.2014.50.7.2177904