Genetic and phenotypic heterogenity of mucopolysaccharidoses

Mucopolysacharidoses (MPS) are genetic disorders caused by the deficiency of specific lysosomal enzymes involved in the degradation of the glycosaminoglycans. They result in a wide range of clinical symptoms, including hepatosplenomegaly, dysostosis multiplex, coarse facial features, hearing loss, visual impairment, upper airway obstruction, restrictive lung disease, valvular heart disease, arthropathy, communicating hydrocephalus and spinal cord compression. Clinical manifestations range from mild somatic changes, normal intelligence and lifespan to severe multiple system involvement, including central nervous system complications and significantly shortened lifespan. The identification of mutations in MPS disease genes shows extensive genetic heterogeneity and provides the molecular explanations for the broad range of clinical phenotypes observed. An understanding of the molecular basis of MPS and its correlation to the clinical phenotype can improve prognostic prediction at diagnosis. It also allows carrier testing and genetic counselling, at the same time providing a framework for more accurate evaluation of treatment protocols and the selection of the most appropriate therapy for individual patients.