Calcium and bone homeostasis in heterozygous carrier's of CYP24A1 mutations: A cross-sectional study
Calcium and bone homeostasis in heterozygous carrier's of CYP24A1 mutations: A cross-sectional study
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DOI：
10.1016/j.bone.2015.06.018
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发表时间：
2015-12-01
期刊：
影响因子：
4.1
通讯作者：
Bouillon, R.
中科院分区：
文献类型：
--
作者：
Cools, M.;Goemaere, S.;Bouillon, R.
背景资料：双等位基因CYP 24 A1突变可引起特发性婴儿高钙血症（IIH）、成人型肾钙质沉着症，并可能引起骨代谢紊乱。目前尚不清楚杂合子携带者是否会出现临床问题或生化异常。我们的目标是深入了解CYP 24 A1杂合子的生化特征和健康问题。研究设计：对参与者进行横断面评估。以前报告的数据载体review.Setting和参与者：三级医院门诊。参与者是一名婴儿的8名家庭成员，该婴儿具有充分表征的纯合CYP 24 A1突变c.1186C > Tp。（Arg 396 Trp）.结果：血清维生素D代谢物。高钙血症、高钙尿症或肾钙质沉着症的症状或生化体征。骨健康在杂合子相比，野生型（WT）subjects.Measurements：基因分型桑格测序;维生素D代谢物液相色谱串联质谱法;肾，钙和骨标志物的生化分析;肾钙质沉着症的肾超声的存在;骨健康双能X射线吸收测定法和外周定量computedtomato.Results：6名参与者是杂合子携带者的突变。杂合子受试者均未发生IIH。其中一人有肾结石病史，另外两人的主诉与诊断相符。未发现WT和杂合子受试者在骨健康、血清或尿钙或25 OHD/24，25（OH）2D比值方面存在重大差异。文献报告了33例杂合子IIH病例中的3例。在所有三个中，25 OHD/24，25（OH）2D比率高度升高。肾钙质沉着症是经常报告的家族成员IIH cases.Limitations：小样本量，缺乏一个大的对照group.Conclusions：我们和文献数据表明，大多数杂合子CYP 24 A1突变携带者有一个正常的25 OHD/24，25（OH）2D的比例，通常是无症状的，有一个正常的骨骼状态，但可能是在肾钙质沉着症的风险增加。对现有文献的回顾表明，无论携带者状态如何，25 OHD/24，25（OH）2D比值升高可能与IHH症状相关。(C)2015 Elsevier Inc. All rights reserved.
Background: Bi-allelic CYP24A1 mutations can cause idiopathic infantile hypercalcemia (IIH), adult-onset nephrocalcinosis, and possibly bone metabolism disturbances. It is currently unclear if heterozygous carriers experience clinical problems or biochemical abnormalities. Our objective is to gain insight in the biochemical profile and health problems in CYP24A1 heterozygotes.Study design: Cross-sectional evaluation of participants. Data of previously reported carriers are reviewed.Setting and participants: Outpatient clinic of a tertiary care hospital. Participants were eight family members of an infant with a well-characterized homozygous CYP24A1 mutation c.1186C > T p.(Arg396Trp).Outcomes: Serum vitamin D metabolites. Symptoms or biochemical signs of hypercalcemia, hypercalciuria or nephrocalcinosis. Bone health in heterozygous as compared to wild type (WT) subjects.Measurements: Genotyping by Sanger sequencing; vitamin D metabolites by liquid chromatography tandem mass spectrometry; renal, calcium and bone markers by biochemical analyses; presence of nephrocalcinosis by renal ultrasound; bone health by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography.Results: Six participants were heterozygous carriers of the mutation. None of the heterozygous subjects had experienced IIH. One had a documented history of nephrolithiasis, two others had complaints compatible with this diagnosis. No major differences between WT and heterozygous subjects were found regarding bone health, serum or urinary calcium or 25OHD/24,25(OH)2D ratio. Literature reports on three out of 33 heterozygous cases suffering from IIH. In all three, the 25OHD/24,25(OH)2D ratio was highly elevated. Nephrocalcinosis was frequently reported in family members of IIH cases.Limitations: Small sample size, lack of a large control group.Conclusions: Our and literature data suggest that most heterozygous CYP24A1 mutation carriers have a normal 25OHD/24,25(OH)2D ratio, are usually asymptomatic and have a normal skeletal status but may possibly be at increased risk of nephrocalcinosis. A review of the available literature suggests that an elevated 25OHD/24,25(OH)2D ratio may be associated with symptoms of IHH, irrespective of carrier status. (C) 2015 Elsevier Inc. All rights reserved.