The problem of rickets in UK Asians

A large body of work relating to the occurrence of rickets in UK Asians is reviewed. Several theories of the aetiology of this condition are shown to be untenable: it is not exclusively a function of sunlight deprivation or of darker pigmentation; nor is it simply due to phytate-induced losses of calcium from the gut. Asian rickets, however, is associated with a high consumption of cereals, and experiments with rats have suggested a mechanism. In the absence of adequate vitamin D from sunlight, the low-calcium, high cereal intake of the UK Asian population may induce a state of mild secondary hyperparathyroidism which enhances the destruction of vitamin D and leads to a progressive reduction in vitamin D status and, ultimately, to the development of clinical rickets.     

骨骼畸形儿童的临床研究

目的探讨骨骼畸形与晚发性佝偻病(DR)的关系.方法采用病例对照,结合临床调查,检测了85例骨骼畸形儿童及50例健康儿童的血钙、血磷、碱性磷酸酶(ALP)、骨碱性磷酸酶(BALP)、X线.结果85例5～16岁骨骼畸形儿童的临床症状主要为多汗、肢体疼痛、肢体无力、肌肉痉挛;体征以鸡胸和X形腿为多见;血钙、血磷、碱性磷酸酶检测阳性率均低,BALP测定阳性率(BALP>250U/L)为14.1%,诊断为DR,并与对照组比较,差异有显著性意义(p<0.05).结论要重视骨骼畸形儿童的诊断及DR的诊断和防治工作.     

Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies

Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

迟发性佝偻病与支气管哮喘

目的 观察迟发性佝偻病并发哮喘的治疗反应,探讨维生Ｄ（ＶＤ）缺乏的哮喘发病中的作用。方法 ３１例迟发性佝偻病并发哮喘患儿随机分成Ａ、Ｂ两组,１５例单纯哮喘患儿为Ｃ组。３组均吸入二丙酸倍氯米松气雾剂（ｂｅｃｏｔｉｄｅ ｉｎｈａｌｅｒ）１年,Ａ组另加ＶＤ３治疗。于治疗前后别测定肺功能等。结果 治疗前３组用力呼气一秒量（ＦＥＶ１．０）及用力呼气峰流速（ＰＥＦ）均减低,但组间无差别;Ａ、Ｂ两组骨钙素和反映     

Phosphate transport in osteoblasts from normal and X-linked hypophosphatemic mice

Human hypophosphatemic vitamin D-resistant rickets (X-linked hypophosphatemia-XLH) is characterized by hypophosphatemia, a decreased tubular reabsorption of phosphate (P_i) and defective skeleton mineralization. Utilizing a mouse model (Hyp) of XLH, which demonstrates biological abnormalities and skeletal defects of XLH, we analyzed sodium-dependent phosphate transport in isolated osteoblasts derived from the calvaria of normophosphatemic and hypophosphatemic mice. Initial rates of phosphate uptake by normal and Hyp osteoblasts showed similar slopes. Osteoblasts from both normal and Hyp mice exhibited saturable, sodium-dependent phosphate transport with apparent V_max and K_m values not significantly different (normal mice, V_max=24.30±3.45 nmol/mg prot. 10 min, K_m=349.49±95.20 mol/liter; Hyp mice, V_max=23.03±3.41 nmol/mg prot. 10 min, K_m=453.64±106.93 mol/liter, n=24). No differences were found in the ability of normal and Hyp osteoblasts to respond to P_i transport after 5 hours of P_i deprivation. Both cell types exhibited a similar increase in cAMP in response to PTH. The accumulated results demonstrate that P_i uptake and transport in normal and Hyp mouse osteoblasts is a sodium-dependent saturable process. As osteoblast P_i uptake and transport is apparently normal in the Hyp mouse model of XLH, the osteoblastic failure described for the Hyp mouse should be attributed to other mechanism(s).     

Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

佝偻病简易诊断与骨X线及实验性诊断的相关性

目的 探讨婴幼儿佝偻病的简易诊断与骨X线、实验性诊断的相关性。方法 对简易诊断为佝偻病的166例小儿全部作骨X线、骨碱性磷酸酶（BALP）,血生化检查。结果 经骨X线确诊为佝偻病78例（47．0％）。BALP检测结果与X线检查结果符合率最高。夜惊、多汗、乒乓头、枕秃在佝偻病患儿中发生率较高。结论 简易诊断具有一定的实用价值,可应用于我国基层卫生机构,若有条件应用骨X线、BALP、血生化测定则可提高佝偻病诊断的准确性。     

儿童维生素D、钙营养与营养性维生素D缺乏性佝偻病判定与评价现状

        儿童维生素D缺乏性佝偻病（vitamin D deficiency,Rickets）是由于维生素D缺乏导致的可预防性疾病,与维生素D和钙营养密切相关。近年来,研究发现非肌肉骨骼系统的疾病,包括癌症、代谢综合征、感染和自身免疫性疾病与维生素D水平不足密切相关［1-3］。由于许多观察性研究证实维生素D不足在世界许多地区普遍存在,包括工业性国家［4-5］。因此,儿童维生素D、钙营养与营养性维生素D缺乏性佝偻病再次受到关注,国内外对儿童维生素D、钙营养与维生素D缺乏性佝偻病的判定和评价也有了新认识。     

150名学龄前儿童佝偻病患病调查及X线与血25(OH)D3水平关系分析

【目的】 了解学龄前儿童佝偻病患病情况及X线与血25(OH)D₃水平关系。 【方法】 2010年1月在省绥化市5所幼儿园和2所学前班儿童中随机抽取150名进行体检、病史采集、采血化验、拍左腕骨正位片,并对数据进行分析。 【结果】 150名儿童中佝偻病患儿52例,患病率为34.6%。患病率与性别及年龄无关。佝偻病患儿中15例出现X改变,其平均血清25(OH)D₃水平与无X线改变患儿比较差异有统计学意义。 【结论】 学龄前儿童佝偻病仍存在,但均为轻度患者;在所调查的150名学龄前儿童中普遍存在维生素D缺乏及不足情况;血清中25(OH)D₃水平越低越可能出现X线骨骼改变。     

Primary Hyperparathyroidism Masquerading as Rickets: Diagnostic Challenge and Treatment Outcomes

Primary hyperparathyroidism (PHPT) is extremely uncommon among children and is more likely to be associated with genetic syndromes, multiglandular involvement, and more severe symptoms. Rickets can very rarely be the presenting feature of PHPT in children. Rickets was diagnosed in a 12-year-old girl presenting with short stature, genu valgum, eversion deformity at the ankle joints, and flat feet. Radiograms showed generalized osteopenia, widening of the distal ends of the long bones along with splaying, cupping and fraying. Biochemical evaluation revealed low serum calcium (7.8 mg/dL), low phosphorus (1.4 mg/dL), vitamin-D deficiency [25-hydroxy-vitamin-D (25(OH)D): 8.7 ng/mL], and elevated intact parathyroid hormone (PTH, 811 pg/mL). Re-evaluation due to lack of clinical improvement following vitamin-D and calcium supplementation revealed hypercalcemia 11.9 mg/dL, normal 25(OH)D 41 ng/mL, persistence of elevated PTH 632 pg/mL. A 99mTc-sestamibi scan showed increased uptake at the lower pole of the right lobe of the thyroid. A right inferior parathyroidectomy was performed. Histopathology revealed chief cell type parathyroid adenoma. Last evaluated 4 months after surgery, the bone pains and proximal weakness had resolved, with significant improvement in the patient’s quality of life. Rickets in the setting of PHPT often masks the classical phenotype of PHPT. In a child with rickets, lack of improvement following vitamin-D supplementation, hypercalcemia at presentation or following vitamin-D supplementation are warning signs which necessitate further evaluation to rule out PHPT.Conflict of interest:None declared.