Hereditary vitamin D-resistant rickets （HVDRR） is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase...Hereditary vitamin D-resistant rickets （HVDRR） is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. This disorder is caused by homogeneous or heterogeneous mutations affecting the function of the vitamin D receptor （VDR）, which lead to complete or partial target organ resistance to the action of 1,25- dihydroxy vitamin D~ A non-consanguineous family of Chinese Han origin with one affected individual demonstrating HVDRR was recruited, with the proband evaluated clinically, biochemically and radiographically. To identify the presence of mutations in the VDR gene, all the exons and exon-intron junctions of the VDR gene from all family members were amplified using PCR and sequenced. The proband showed rickets, progressive alopecia, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. She also suffered from epilepsy, which is rarely seen in patients with HVDRR. Direct sequencing analysis revealed a homozygous missense mutation c.122G 〉 A （p.C41Y） in the VDR gene of the proband, which is located in the first zinc finger of the DNA-binding domain. Both parents had a normal phenotype and were found to be heterozygous for this mutation. We report a Chinese Han family with one individual affected with HVDRR. A homozygous missense mutation c.122G 〉 A （p.C41Y） in the VDR gene was found to be responsible for the patient＇s syndrome. In contrast to the results of treatment of HVDRR in other patients, our patient responded well to a supplement of oral calcium and a low dose of calcitriol.展开更多
Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormalit...Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographicaUy. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone （PTH）, 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient＇s CaSR gene revealed a new missense mutation （c.2279T 〉 A） in exon 7, leading to the damaging amino change （p.I760N） in the mature CaSR protein, confirming the diagnosis of ~H. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated ~H levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that CaSR mutations may have a partial role in the pathogenesis of skeletal deformities.展开更多
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
目的观察维生素K对儿童营养性维生素D缺乏性佝偻病(rickets of vitamin D deficiency,VDDR)的影响。方法选取2023年4月至2024年4月我院儿科收治的VDDR患儿100例,随机分为对照组(n=50,口服维生素D)和研究组(n=50,口服维生素D、K4),两组...目的观察维生素K对儿童营养性维生素D缺乏性佝偻病(rickets of vitamin D deficiency,VDDR)的影响。方法选取2023年4月至2024年4月我院儿科收治的VDDR患儿100例,随机分为对照组(n=50,口服维生素D)和研究组(n=50,口服维生素D、K4),两组均连续用药2周。比较两组骨密度(bone mineral density,BMD)、骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,B-ALP)、骨钙素(osteocalcin,OC)、羧化不全OC(undercarboxylated osteocalcin,ucOC)、前列腺素(prostaglandin,PG)E2、肿瘤坏死因子(tumor necrosis factor-α,TNF)-α、白介素(interleukin,IL)-1β及不良反应发生情况。结果治疗后,两组桡骨、尺骨BMD均高于治疗前(P<0.05),且研究组高于对照组(P<0.05)。治疗后,两组B-ALP、OC、ucOC、PGE2、TNF-α及IL-1β水平均低于治疗前(P<0.05),且研究组小于对照组(P<0.05)。两组不良反应总发生率差异无统计学意义(P>0.05)。结论维生素K可改善VDDR患儿BMD,调节B-ALP、骨钙素、ucOC、PGE2、TNF-α及IL-1β水平,且未增加不良反应发生风险。展开更多
基金supported by a grant from The Ministry of Science and Technology of the People’s Republic of China(National Science and Technology Major Projects for "Major New Drugs Innovation and Development" 2008ZX09312-016)National Natural Science Foundation of China (no.81070687 and 81170805)+2 种基金Beijing Natural Science Foundation (no.7121012)Scientific Research Foundation of Beijing Medical Development (no.2007-3029)National Key Program of Clinical Science (WBYZ2011-873)
文摘Hereditary vitamin D-resistant rickets （HVDRR） is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. This disorder is caused by homogeneous or heterogeneous mutations affecting the function of the vitamin D receptor （VDR）, which lead to complete or partial target organ resistance to the action of 1,25- dihydroxy vitamin D~ A non-consanguineous family of Chinese Han origin with one affected individual demonstrating HVDRR was recruited, with the proband evaluated clinically, biochemically and radiographically. To identify the presence of mutations in the VDR gene, all the exons and exon-intron junctions of the VDR gene from all family members were amplified using PCR and sequenced. The proband showed rickets, progressive alopecia, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated alkaline phosphatase. She also suffered from epilepsy, which is rarely seen in patients with HVDRR. Direct sequencing analysis revealed a homozygous missense mutation c.122G 〉 A （p.C41Y） in the VDR gene of the proband, which is located in the first zinc finger of the DNA-binding domain. Both parents had a normal phenotype and were found to be heterozygous for this mutation. We report a Chinese Han family with one individual affected with HVDRR. A homozygous missense mutation c.122G 〉 A （p.C41Y） in the VDR gene was found to be responsible for the patient＇s syndrome. In contrast to the results of treatment of HVDRR in other patients, our patient responded well to a supplement of oral calcium and a low dose of calcitriol.
基金supported by the National Natural Science Foundation of China(nos.81070687 and 81170805)Beijing Natural Science Foundation(no.7121012)+2 种基金Ministry of Science and Technology of the People’s Republic of China(National Science and Technology Major Projects for‘Major New Drugs Innovation and Development 2008ZX09312-016)Scientific Research Foundation of Beijing Medical Development(no.2007-3029)National Key Program of Clinical Science(WBYZ2011-873)
文摘Familial hypocalciuric hypercalcemia （FHH） is caused by inactivating mutations in the calcium-sensing receptor （CaSR） gene. The loss of function of CaSR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographicaUy. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone （PTH）, 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient＇s CaSR gene revealed a new missense mutation （c.2279T 〉 A） in exon 7, leading to the damaging amino change （p.I760N） in the mature CaSR protein, confirming the diagnosis of ~H. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated ~H levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that CaSR mutations may have a partial role in the pathogenesis of skeletal deformities.
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.
文摘目的观察维生素K对儿童营养性维生素D缺乏性佝偻病(rickets of vitamin D deficiency,VDDR)的影响。方法选取2023年4月至2024年4月我院儿科收治的VDDR患儿100例,随机分为对照组(n=50,口服维生素D)和研究组(n=50,口服维生素D、K4),两组均连续用药2周。比较两组骨密度(bone mineral density,BMD)、骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,B-ALP)、骨钙素(osteocalcin,OC)、羧化不全OC(undercarboxylated osteocalcin,ucOC)、前列腺素(prostaglandin,PG)E2、肿瘤坏死因子(tumor necrosis factor-α,TNF)-α、白介素(interleukin,IL)-1β及不良反应发生情况。结果治疗后,两组桡骨、尺骨BMD均高于治疗前(P<0.05),且研究组高于对照组(P<0.05)。治疗后,两组B-ALP、OC、ucOC、PGE2、TNF-α及IL-1β水平均低于治疗前(P<0.05),且研究组小于对照组(P<0.05)。两组不良反应总发生率差异无统计学意义(P>0.05)。结论维生素K可改善VDDR患儿BMD,调节B-ALP、骨钙素、ucOC、PGE2、TNF-α及IL-1β水平,且未增加不良反应发生风险。
