Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology.

摘要: Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive inherited disease, caused by deficiency of the enzyme α-L-iduronidase, resulting in accumulation glycosaminoglycans (GAGs) dermatan and heparan sulfate organs tissues. If untreated, patients with severe phenotype die within first decade life. Early diagnosis crucial to prevent development fatal disease manifestations, prominently cardiac respiratory as well cognitive impairment. However, initial symptoms are nonspecific impede early diagnosis. This review discusses common phenotypic manifestations order which they develop. Similarities differences three animal models for MPS highlighted. Earliest symptoms, present during 6 months life, include hernias, coarse facial features, recurrent rhinitis and/or upper airway obstructions absence infection, thoracolumbar kyphosis. During next months, loss hearing, corneal clouding, further musculoskeletal dysplasias Finally, late including lower decline emerge. Cardiac can develop infancy. The underlying pathogenesis intra- extracellular partially degraded GAGs infiltration cells enlarged lysosomes causing tissue expansion bone deformities. These interfere proper arrangement collagen fibrils, disrupt nerve fibers, cause devastating secondary pathophysiological cascades inflammation, oxidative stress, other disruptions intracellular homeostasis. A greater understanding natural history will allow timely management facilitating better treatment outcomes.