Mucopolysaccharidosis type I (MPSI) (OMIM #252800) is an autosomal recessive disorder caused by pathogenic variants in the IDUA gene encoding for the lysosomal alpha-L-iduronidase enzyme. The deficiency of this enzyme causes systemic accumulation of glycosaminoglycans (GAGs). Although disease manifestations are typically not apparent at birth, they can present early in life, are progressive, and include a wide spectrum of phenotypic findings. Among these, the storage of GAGs within the lysosomes disrupts cell function and metabolism in the cartilage, thus impairing normal bone development and ossification. Skeletal manifestations of MPSI are often refractory to treatment and severely affect patients’ quality of life. This review discusses the pathological and molecular processes leading to impaired endochondral ossification in MPSI patients and the limitations of current therapeutic approaches. Understanding the underlying mechanisms responsible for the skeletal phenotype in MPSI patients is crucial, as it could lead to the development of new therapeutic strategies targeting the skeletal abnormalities of MPSI in the early stages of the disease.

De Ponti, G., Donsante, S., Frigeni, M., Pievani, A., Corsi, A., Bernardo, M., et al. (2022). MPSI Manifestations and Treatment Outcome: Skeletal Focus. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(19) [10.3390/ijms231911168].

MPSI Manifestations and Treatment Outcome: Skeletal Focus

Serafini M
2022

Abstract

Mucopolysaccharidosis type I (MPSI) (OMIM #252800) is an autosomal recessive disorder caused by pathogenic variants in the IDUA gene encoding for the lysosomal alpha-L-iduronidase enzyme. The deficiency of this enzyme causes systemic accumulation of glycosaminoglycans (GAGs). Although disease manifestations are typically not apparent at birth, they can present early in life, are progressive, and include a wide spectrum of phenotypic findings. Among these, the storage of GAGs within the lysosomes disrupts cell function and metabolism in the cartilage, thus impairing normal bone development and ossification. Skeletal manifestations of MPSI are often refractory to treatment and severely affect patients’ quality of life. This review discusses the pathological and molecular processes leading to impaired endochondral ossification in MPSI patients and the limitations of current therapeutic approaches. Understanding the underlying mechanisms responsible for the skeletal phenotype in MPSI patients is crucial, as it could lead to the development of new therapeutic strategies targeting the skeletal abnormalities of MPSI in the early stages of the disease.
Articolo in rivista - Articolo scientifico
endochondral bone formation; glycosaminoglycans; lysosomal alpha-L-iduronidase; lysosomal storage disease; mucopolysaccharidoses; mucopolysaccharidosis type I;
English
22-set-2022
2022
23
19
11168
open
De Ponti, G., Donsante, S., Frigeni, M., Pievani, A., Corsi, A., Bernardo, M., et al. (2022). MPSI Manifestations and Treatment Outcome: Skeletal Focus. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(19) [10.3390/ijms231911168].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/459448
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