Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology
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 di...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1838 |
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| author | Christiane S. Hampe Julie B. Eisengart Troy C. Lund Paul J. Orchard Monika Swietlicka Jacob Wesley R. Scott McIvor |
| author_facet | Christiane S. Hampe Julie B. Eisengart Troy C. Lund Paul J. Orchard Monika Swietlicka Jacob Wesley R. Scott McIvor |
| author_sort | Christiane S. Hampe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:57:41Z |
| format | Article |
| id | doaj.art-2b5b1cd767f54850a959135cf7367b3d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T17:57:41Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2b5b1cd767f54850a959135cf7367b3d2023-11-20T09:08:23ZengMDPI AGCells2073-44092020-08-0198183810.3390/cells9081838Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular PathologyChristiane S. Hampe0Julie B. Eisengart1Troy C. Lund2Paul J. Orchard3Monika Swietlicka4Jacob Wesley5R. Scott McIvor6Immusoft Corp, Seattle, WA 98103, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USADepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USAImmusoft Corp, Seattle, WA 98103, USAImmusoft Corp, Seattle, WA 98103, USAImmusoft Corp, Minneapolis, MN 55413, USAMucopolysaccharidosis 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.https://www.mdpi.com/2073-4409/9/8/1838mucopolysaccharidosis type Ianimal modelsα-L-iduronidase |
| spellingShingle | Christiane S. Hampe Julie B. Eisengart Troy C. Lund Paul J. Orchard Monika Swietlicka Jacob Wesley R. Scott McIvor Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology Cells mucopolysaccharidosis type I animal models α-L-iduronidase |
| title | Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology |
| title_full | Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology |
| title_fullStr | Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology |
| title_full_unstemmed | Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology |
| title_short | Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology |
| title_sort | mucopolysaccharidosis type i a review of the natural history and molecular pathology |
| topic | mucopolysaccharidosis type I animal models α-L-iduronidase |
| url | https://www.mdpi.com/2073-4409/9/8/1838 |
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