Abstract
Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.
Highlights
Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA)
hematopoietic stem cell transplantation (HSCT) performed in young MPS I cats resulted in significant increases in IDUA activity in liver, spleen, lung, and thyroid, but not in kidney, brain, or heart
Transplantation at a later age (8 weeks) resulted in overcorrection of the reduced osteoclastogenesis described in untreated IDUA-deficient mice, which was corrected with combined HSCT and enzyme replacement therapy (ERT) [140]
Summary
Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). Approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Treatment must commence as early as possible for maximum effect and diagnostic delay-due to the nonspecific nature of early symptoms-limits treatment success [1]. To overcome this limitation, implementation of MPS I in newborn screening programs is strongly recommended [2,3]. Biomolecules 2021, 11, 189 of experimental strategies are currently under development to reduce the remaining burden of disease
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