Rafaelsen Silje, Johansson Stefan, Ræder Helge, Bjerknes Robert
Section for PediatricsDepartment of Clinical Science, Haukeland University Hospital, University of Bergen, N-5021 Bergen, NorwayCenter for Medical Genetics and Molecular MedicineDepartment of PediatricsHaukeland University Hospital, Bergen, Norway
Section for PediatricsDepartment of Clinical Science, Haukeland University Hospital, University of Bergen, N-5021 Bergen, NorwayCenter for Medical Genetics and Molecular MedicineDepartment of PediatricsHaukeland University Hospital, Bergen, Norway Section for PediatricsDepartment of Clinical Science, Haukeland University Hospital, University of Bergen, N-5021 Bergen, NorwayCenter for Medical Genetics and Molecular MedicineDepartment of PediatricsHaukeland University Hospital, Bergen, Norway.
Eur J Endocrinol. 2016 Feb;174(2):125-36. doi: 10.1530/EJE-15-0515. Epub 2015 Nov 5.
Hereditary hypophosphatemias (HH) are rare monogenic conditions characterized by decreased renal tubular phosphate reabsorption. The aim of this study was to explore the prevalence, genotypes, phenotypic spectrum, treatment response, and complications of treatment in the Norwegian population of children with HH.
Retrospective national cohort study.
Sanger sequencing and multiplex ligand-dependent probe amplification analysis of PHEX and Sanger sequencing of FGF23, DMP1, ENPP1KL, and FAM20C were performed to assess genotype in patients with HH with or without rickets in all pediatric hospital departments across Norway. Patients with hypercalcuria were screened for SLC34A3 mutations. In one family, exome sequencing was performed. Information from the patients' medical records was collected for the evaluation of phenotype.
Twety-eight patients with HH (18 females and ten males) from 19 different families were identified. X-linked dominant hypophosphatemic rickets (XLHR) was confirmed in 21 children from 13 families. The total number of inhabitants in Norway aged 18 or below by 1st January 2010 was 1,109,156, giving an XLHR prevalence of ∼1 in 60,000 Norwegian children. FAM20C mutations were found in two brothers and SLC34A3 mutations in one patient. In XLHR, growth was compromised in spite of treatment with oral phosphate and active vitamin D compounds, with males tending to be more affected than females. Nephrocalcinosis tended to be slightly more common in patients starting treatment before 1 year of age, and was associated with higher average treatment doses of phosphate. However, none of these differences reached statistical significance.
We present the first national cohort of HH in children. The prevalence of XLHR seems to be lower in Norwegian children than reported earlier.
遗传性低磷血症（HH）是一种罕见的单基因疾病，其特征为肾小管磷重吸收减少。本研究旨在探讨挪威儿童HH患者的患病率、基因型、表型谱、治疗反应及治疗并发症。
全国性回顾性队列研究。
对挪威所有儿科医院科室中患有或未患佝偻病的HH患者进行PHEX的桑格测序和多重配体依赖性探针扩增分析，以及FGF23、DMP1、ENPP1KL和FAM20C的桑格测序。对高钙尿症患者筛查SLC34A3突变。在一个家庭中进行了外显子组测序。收集患者病历信息以评估表型。
共识别出来自19个不同家庭的28例HH患者（18例女性和10例男性）。13个家庭的21名儿童被确诊为X连锁显性低磷性佝偻病（XLHR）。截至2010年1月1日，挪威18岁及以下居民总数为1,109,156人，XLHR在挪威儿童中的患病率约为1/60,000。在两名兄弟中发现了FAM20C突变，一名患者中发现了SLC34A3突变。在XLHR患者中，尽管使用口服磷酸盐和活性维生素D化合物进行治疗，但生长仍受到影响，男性受影响的程度往往比女性更大。肾钙质沉着症在1岁前开始治疗的患者中似乎略为常见，并且与较高的磷酸盐平均治疗剂量相关。然而，这些差异均未达到统计学意义。
我们展示了首个全国性的儿童HH队列。挪威儿童中XLHR的患病率似乎低于先前报道。
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