Mucopolysaccharidoses
Objectives- Describe the common feature of all the mucopolysaccharidoses
- Describe the genetic transmission of the mucopolysaccharidoses
- Describe the organ systems involved in the different phenotypic expressions of the mucopolysaccharidoses
Discussion points
- What is a mucopolysaccharide?
- Would it be logical to call this family of disorders lysozomal storage disease? Why are the lysozomes enlarged?
- What relationship does infantile kyphosis have with the mucopolysaccharidoses?
- How is the diagnosis of a mucopolysaccharidosis presently established?
Discussion
The mucopolysaccharidoses are a family of rare genetic disorders all characterized by a defect in degradation of proteoglycans. A recent study in Northern Ireland estimated the overall incidence of mucopolysaccharidoses as 1: 25,000 live births. The term mucopolysaccharide would be obsolete were it not fixed to these disorders, as the macromolecules formerly known as mucopolysaccharides or protein-polysaccharides are now called proteoglycans. They consist of a protein core with covalently bound polysaccharide (glysoaminoglycan) chains. Examples of glysoaminoglycans are chondroitin sulfates 4 and 6, keratan sulfate, heparin sulfate, and dermatan sulfate. Proteoglycans are normally degraded in the cell by lysozomes, an enzyme dependant process. Absence of deficiency of any necessary enzyme will result in an accumulation of proteoglycans in the intracellular lysozomes. Urinary excretion of excess amounts of the undegraded glysoaminoglycan is diagnostic. The resulting phenotype depends on the specific enzyme deficiency, with varying effects on the skeletal, ocular, visceral organs, or central nervous system. Two of the more severe forms of the mucopolysaccharidoses, Hunter and Hurler syndromes, may be suspected by noting infantile kyphosis. Morquio syndrome also has significant associated orthopaedic problems, consisting of short stature, kyphosis, and genu valgum. Stiff joints and short stature are features of Maroteaux-Lamy syndrome. All the mucopolysaccharidoses are transmitted by recessive inheritance, X-linked for Hunter and autosomal for the rest.
References
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- Byers S, Rozaklis T, Brumfield LK, Ranieri E, Hopwood JJ. Glycosaminoglycan accumulation and excretion in the mucopolysaccharidoses: characterization and basis of a diagnostic test for MPS. Molecular Genetics & Metabolism 1998; 65( 4): 282-90.
- Gamble JG. The musculoskeletal system. Physiological basis. New York: Raven Press; 1988.
- Levin TL, Berdon WE, Lachman RS, Anyane-Yeboa K, Ruzal-Shapiro C, Roye DP, Jr. Lumbar gibbus in storage diseases and bone dysplasias. Pediatric Radiology 1997; 27( 4): 289-94.
- Mankin HJ, Mow VC, Buckwalter JA, Iannotti JP, Ratcliffe A. Articular cartilage structure, composition, and function. In: Buckwalter JA, Einhorn TA, Simon SR, editors. Orthopaedic Basic Science. Biology and Biomechanics of the Musculoskeletal System: American Academy of Orthopaedic Surgeons; 2000.
- Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Human Genetics 1997; 101( 3): 355-8.
May 16-19, 2012 in Denver, CO
