Mutation update and long-term outcome after treatment with active vitamin D3 in Chinese patients with pseudovitamin D-deficiency rickets (PDDR)
Mutation update and long-term outcome after treatment with active vitamin D3 in Chinese patients with pseudovitamin D-deficiency rickets (PDDR)
复制标题
中国假性维生素 D 缺乏性佝偻病 (PDDR) 患者接受活性维生素 D-3 治疗后的突变更新和长期结果
DOI：
10.1007/s00198-018-4607-5
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Xia, W.
中科院分区：
文献类型：
--
作者：
Chi, Y.;Sun, J.;Xia, W.
假维生素D缺乏症是由细胞色素P27B1引起的一种罕见疾病。在这项研究中，我们在7名PDDR患者中发现了9个突变。此外，我们还观察了15例PDDR患者对骨化三醇长期治疗的反应，结果表明，经过1年的治疗，生化异常已得到满意的纠正。介绍假性维生素D缺乏症是一种罕见的常染色体隐性遗传病，由25-羟基维生素D-1-羟基酶缺陷引起，该基因由CYP27B1编码。本研究的目的是确定中国PDDR患者的细胞色素P27B1基因突变，并探讨骨化三醇长期治疗的疗效。方法对6个家系的7名个体进行细胞色素P27B1基因突变的检测。结果发现9个不同的突变：2个新的错义突变(G194R，R259L)，3个新的和1个已报道的缺失突变(c1442delA，c1504delA，c311-321del和c.48-60del)，2个新的无义突变(c.85G>；T，c.580G>；T)和1个已报道的插入突变(c第1325-1332insCCCACCC)。统计学分析显示，甲状旁腺激素(PTH)和碱性磷酸酶(ALP)分别在骨化三醇治疗6个月和1年后显著下降。对所有无肾结石记录的患者进行尿钙测定。经过6年的治疗，放射学异常也有所改善。2例已达终末身高的患者均为矮小(身高Z评分低于-2.0)。结论我们在7个中国PDDR家系中发现了7个新突变。结果显示，活性维生素D-3治疗1年后，甲状旁腺素和碱性磷酸酶显著下降。生化异常的矫正并未令人满意地提高最终身高。
A Summary Pseudovitamin D-deficiency rickets is a rare disease which is caused by CYP27B1. In this study, we identified 9 mutations in 7 PDDR patients. In addition, we observed the response to long-term treatment of calcitriol in 15 Chinese patients with PDDR, which showed that the biochemical abnormalities had been corrected satisfactorily after 1-year treatment.Introduction Pseudovitamin D-deficiency rickets is a rare autosomal recessive disorder resulting from a defect in 25-hydroxyvitamin D 1-hydroxylase, which is encoded by CYP27B1. The purpose of this study was to identify the CYP27B1 mutations and investigate the response to long-term treatment of calcitriol in Chinese patients with PDDR.Methods We investigated CYP27B1 mutations in seven individuals from six separate families. To investigate the response to long-term (13 years) treatment with calcitriol in PDDR patients, we additionally collected clinical data of eight families from our previous report and analyzed their biochemical parameter and radiographic changes during the treatment.Results Nine different mutations were identified: two novel missense mutations (G194R, R259L), three novel and one reported deletion mutations (c1442delA, c1504delA, c311-321del, and c.48-60del), two novel nonsense mutations (c.85G>T, c.580G>T), and a reported insertion mutation (c1325-1332insCCCACCC). The statistical analysis revealed that parathyroid hormone (PTH) and ALP significantly decreased after 6-month and 1-year treatment with calcitriol respectively. Urine calcium was measured in all the patients without kidney stones being documented. After 6-year treatment, the radiographic abnormalities had also been improved. Two patients who had reached their final height are both with short stature (height Z-score below -2.0).Conclusions We identified seven novel mutations of CYP27B1 gene in seven Chinese PDDR families. Our findings revealed after 1-year treatment of active vitamin D-3, PTH and ALP significantly decreased. The correction of the biochemical abnormalities had not improved the final height satisfactorily.