Failures of Endochondral Ossification in the Mucopolysaccharidoses

Jiang, Zhirui; Byers, Sharon; Casal, Margret L.; Smith, Lachlan J.

doi:10.1007/s11914-020-00626-y

Cited by 21 publications

(22 citation statements)

References 184 publications

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“…This seems to be related to the widely described detrimental effects of the pathologic accumulation of GAGs in the bones and growth plates [ 18 , 19 ], likely related in part to the avascular nature of growth plate cartilage making this tissue less accessible to therapeutic agents. Indeed, several Authors highlighted that the poor correction of short stature in MPS patients receiving HSCT could be related to its inability to normalize endochondral ossification (typically affected in MPS) due to poor cell engraftment and enzyme access to cartilage of the growth plates [ 9 , 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients”

Cattoni

Chiaraluce

Gasperini

et al. 2021

Molecular Genetics and Metabolism Reports

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The impact of hematopoietic stem cell transplantation (HSCT) on growth in patients diagnosed with mucopolysaccharidosis I Hurler (MPS-IH) has been historically regarded as unsatisfactory. Nevertheless, the growth patterns recorded in transplanted patients have always been compared to those of healthy children. The objective of this study was to verify the impact of HSCT on MPS-IH long term growth achievements. The auxological data of 15 patients were assessed longitudinally and compared both to the WHO growth centiles for healthy individuals and to recently published curves of untreated MPS-IH children. Despite a progressive decrease after HSCT when estimated with reference to the WHO growth charts, median height SDS showed a progressive and statistically significant increase when comparing the stature recorded at each timepoint in our population to the curves of untreated MPS-IH individuals (from ‐0.39 SDS at t 0 to +1.35 SDS 5 years after HSCT, p value < 0.001 and to +3.67 SDS at the age of 9 years, p value < 0.0001 ). In conclusion, though not efficient enough to restore a normal growth pattern in MPS-IH patients, we hereby demonstrate that HSCT positively affects growth and provides transplanted patients with a remarkable height gain compared to untreated gender- and age- matched individuals.

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Section: Introductionmentioning

confidence: 99%

“Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients”

Cattoni

Chiaraluce

Gasperini

et al. 2021

Molecular Genetics and Metabolism Reports

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“…This may lead to impaired fusion of lysosomes with autophagosomes and impaired autophagy, in addition to oxidative stress and apoptosis 41,66 . Indeed, abnormal autophagy and increased amounts of autophagosomes have been demonstrated in several animal models of MPS 85 …”

Section: Challenges In Treating Mps I Bone Disease: Pathophysiologymentioning

confidence: 99%

MPS I: Early diagnosis, bone disease and treatment, where are we now?

Kingma

Jonckheere

2021

J of Inher Metab Disea

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Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by α‐L‐iduronidase deficiency. Patients present with a broad spectrum of disease severity ranging from the most severe phenotype (Hurler) with devastating neurocognitive decline, bone disease and early death to intermediate (Hurler‐Scheie) and more attenuated (Scheie) phenotypes, with a normal life expectancy. The most severely affected patients are preferably treated with hematopoietic stem cell transplantation, which halts the neurocognitive decline. Patients with more attenuated phenotypes are treated with enzyme replacement therapy. There are several challenges to be met in the treatment of MPS I patients. First, to optimize outcome, early recognition of the disease and clinical phenotype is needed to guide decisions on therapeutic strategies. Second, there is thus far no effective treatment available for MPS I bone disease. The pathophysiological mechanisms behind bone disease are largely unknown, limiting the development of effective therapeutic strategies. This article is a state of the art that comprehensively discusses three of the most urgent open issues in MPS I: early diagnosis of MPS I patients, pathophysiology of MPS I bone disease, and emerging therapeutic strategies for MPS I bone disease.

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“…The serum concentrations of BSAP and osteocalcin reflect the cellular activity of osteoblasts [ 26 , 27 , 28 , 29 ]. The serum concentrations of the carboxy-terminal and amino-terminal pro-peptides of type I procollagen (PICP and PINP, respectively) reflect changes in the synthesis of new collagen.…”

Section: Physiology Of Normal Bone Development and Remodelingmentioning

confidence: 99%

“…Several previous reports have demonstrated that growth plates in MPS commonly exhibit abnormalities, including enlarged and vacuole-filled chondrocytes, disorganized columnar architecture in the PZ and HZ, and reduced calcification of cartilage tissue [ 28 , 31 , 32 ] ( Table 1 ). Similar histopathological findings were observed in animal models of MPS.…”

Section: Pathophysiology Related To Bone Metabolism In Mpsmentioning

confidence: 99%

Bone Biomarkers in Mucopolysaccharidoses

Nakamura-Utsunomiya

2021

IJMS

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The accumulation of glycosaminoglycans (GAGs) in bone and cartilage leads to progressive damage in cartilage that, in turn, reduces bone growth by the destruction of the growth plate, incomplete ossification, and growth imbalance. The mechanisms of pathophysiology related to bone metabolism in mucopolysaccharidoses (MPS) include impaired chondrocyte function and the failure of endochondral ossification, which leads to the release of inflammatory cytokines via the activation of Toll-like receptors by GAGs. Although improvements in the daily living of patients with MPS have been achieved with enzyme replacement, treatment for the bone disorder is limited. There is an increasing need to identify biomarkers related to bone and cartilage to evaluate the progressive status and to monitor the treatment of MPS. Recently, new analysis methods, such as proteomic analysis, have identified new biomarkers in MPS. This review summarizes advances in clinical bone metabolism and bone biomarkers.

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Failures of Endochondral Ossification in the Mucopolysaccharidoses

Cited by 21 publications

References 184 publications

“Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients”

“Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients”

MPS I: Early diagnosis, bone disease and treatment, where are we now?

Bone Biomarkers in Mucopolysaccharidoses

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