One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a...One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a “de novo” XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.展开更多
Background Hypophosphatemic rickets/osteomalacia is a group of diseases characterised by defective mineralization of bone due to hypophosphatemia and low 1,25-dihydroxy vitamin D. To explore the role of fibroblast gro...Background Hypophosphatemic rickets/osteomalacia is a group of diseases characterised by defective mineralization of bone due to hypophosphatemia and low 1,25-dihydroxy vitamin D. To explore the role of fibroblast growth factor 23 （FGF-23） in the regulation of phosphate homeostasis, we measured the circulating concentrations of this growth factor in healthy individuals and in patients with hypophosphatemic rickets/osteomalacia. Methods Nineteen patients with hypophosphatemic rickets/osteomalacia were included in hypophosphatemic group （HP, 12 female and 7 male, mean age was 30 years）, and 19 healthy age-matched individuals served as the control group. Full length FGF-23 fragments were measured by two-site enzyme-linked immunosorbent assay.Results Mean FGF-23 concentrations were significantly higher in the HP group （（87.4±43.6） pg/ml） compared with the control group （（19.2±6.16） pg/ml; P 〈0.001）. In 1 patient with tumour-induced osteomalacia, serum FGF-23 concentrations were 84.1 pg/ml; these concentrations were normalized 2 hours after a hemangiopericytoma resection （7.8 pg/ml）. Subsequently, serum 1,25（OH）2 vitamin D3 concentrations significantly increased from 21.3 pg/ml to 89.3 pg/ml, and serum phosphorus levels were normalized. Conclusions Serum FGF-23 concentrations were markedly elevated in patients with hypophosphatemic rickets. FGF-23 plays an important role in the pathogenesis of hypophosphatemic rickets/osteomalacia.展开更多
Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia （XLH） is a rare hereditary metabolic disease manifesting marked hypophosphatemia, short stature and rickets. Its prevalence is approximately ...Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia （XLH） is a rare hereditary metabolic disease manifesting marked hypophosphatemia, short stature and rickets. Its prevalence is approximately 1 in 20 000. Except early exfoliation of the teeth, there are a few oral findings of XLH described in China. Here we present two cases in one family.展开更多
Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice(PUG), a model of human X-linked hypophosphatemic rickets(XLH), displayed metabolic abnormality in ...Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice(PUG), a model of human X-linked hypophosphatemic rickets(XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus- and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin(OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients.展开更多
文摘One of the major causes of congenital hypophosphatemic rickets is the X-linked hypophosphatemic rickets (XHR), due to a defect on PHEX gene. The XHR increases the renal elimination of phosphate, that condition leads a defective mineralization of bones and also affects the growth in children. Clinical diagnosis should be suspected in children with signs of rickets and hypophosphatemia with normal calcium levels. We describe clinical characteristics and genetic results of four patients diagnosed and treated in our Nephrology Section. All patients have a “de novo” XHR as none familiars are affected. Early diagnosis should be suspected before the bone deformities have been submitted and the growth would have been impaired.
基金This study was supported by National Natural Science Foundation of China （NSFC） （No. 30370781） and Doctoral Fund of Ministry of Education of China （No. 20040023055） The authors state that there are no conflicts of interest in this study.
文摘Background Hypophosphatemic rickets/osteomalacia is a group of diseases characterised by defective mineralization of bone due to hypophosphatemia and low 1,25-dihydroxy vitamin D. To explore the role of fibroblast growth factor 23 （FGF-23） in the regulation of phosphate homeostasis, we measured the circulating concentrations of this growth factor in healthy individuals and in patients with hypophosphatemic rickets/osteomalacia. Methods Nineteen patients with hypophosphatemic rickets/osteomalacia were included in hypophosphatemic group （HP, 12 female and 7 male, mean age was 30 years）, and 19 healthy age-matched individuals served as the control group. Full length FGF-23 fragments were measured by two-site enzyme-linked immunosorbent assay.Results Mean FGF-23 concentrations were significantly higher in the HP group （（87.4±43.6） pg/ml） compared with the control group （（19.2±6.16） pg/ml; P 〈0.001）. In 1 patient with tumour-induced osteomalacia, serum FGF-23 concentrations were 84.1 pg/ml; these concentrations were normalized 2 hours after a hemangiopericytoma resection （7.8 pg/ml）. Subsequently, serum 1,25（OH）2 vitamin D3 concentrations significantly increased from 21.3 pg/ml to 89.3 pg/ml, and serum phosphorus levels were normalized. Conclusions Serum FGF-23 concentrations were markedly elevated in patients with hypophosphatemic rickets. FGF-23 plays an important role in the pathogenesis of hypophosphatemic rickets/osteomalacia.
文摘患者,男,47岁,45年前无明显诱因出现双膝内翻畸形,双腿行走呈“O”型,而后畸形逐渐加重,双下肢酸痛,行走呈“剪刀”步态,需要拄拐。就诊前1年来,患者行走困难,并出现右踝关节疼痛,于2017年7月7日在临沂市人民医院骨科就诊。查体:“剪刀”步态,双膝呈内翻畸形,双大腿、小腿内旋畸形,左下肢长约710 mm.
文摘Hypophosphatemic vitamin D-resistant rickets or X-linked hypophosphatemia （XLH） is a rare hereditary metabolic disease manifesting marked hypophosphatemia, short stature and rickets. Its prevalence is approximately 1 in 20 000. Except early exfoliation of the teeth, there are a few oral findings of XLH described in China. Here we present two cases in one family.
基金supported by National Key Technology Support Program(2011BAI15B02,2012BAI39B01)National Key Basic Research Program of China(2011CB944104)
文摘Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice(PUG), a model of human X-linked hypophosphatemic rickets(XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus- and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin(OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients.
基金上海交通大学医学院转化医学创新基金(第一期)(15ZH1007)%上海交通大学医学院转化医学创新基金(第二期)(15ZH4008)The innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine(15ZH1007)%The innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine(15ZH4008)
