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Review
. 2020 Aug 5;9(8):1838.
doi: 10.3390/cells9081838.

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

Christiane S Hampe  1 , Julie B Eisengart  2 , Troy C Lund  2 , Paul J Orchard  2 , Monika Swietlicka  1 , Jacob Wesley  1 , R Scott McIvor  3   4
Affiliations
Review

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

Christiane S Hampe et al. Cells. .

Abstract

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

Keywords: animal models; mucopolysaccharidosis type I; α-L-iduronidase.

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Conflict of interest statement

C.S.H., M.S., J.W. and R.S.M. are employees of Immusoft Corporation. T.C.L. is a paid consultant of Immusoft Corporation.

Figures

Figure 1
Figure 1
Overview of manifestations affecting respiratory function in mucopolysaccharidosis type I (MPS I).
Figure 2
Figure 2
Overview of manifestations affecting auditory function in MPS I.
Figure 3
Figure 3
Overview of ocular manifestations in MPS I.
Figure 4
Figure 4
Schematic overview of manifestations affecting cardiac function in MPS I.
See this image and copyright information in PMC

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