Wu Bo, Wang Ou, Jiang Yan, Li Mei, Xing Xiaoping, Xia Weibo
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Bone Res. 2017 Jun 27;5:17001. doi: 10.1038/boneres.2017.1. eCollection 2017.
Familial hypocalciuric hypercalcemia (FHH) is caused by inactivating mutations in the calcium-sensing receptor () gene. The loss of function of 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 radiographically. 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 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 FHH. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated PTH 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 mutations may have a partial role in the pathogenesis of skeletal deformities.
家族性低钙血症性高钙血症（FHH）由钙敏感受体（CaSR）基因的失活突变引起。在小鼠中，CaSR功能丧失主要表现为佝偻病这一骨骼异常，但在人类中鲜有报道。本文报告一例16岁患FHH的男孩，其表现出佝偻病的骨骼症状。为确定可能的致病突变，对该患者进行了临床、生化及影像学评估。对患者及其家庭成员进行了基因突变筛查。体格检查发现鸡胸畸形，X线检查显示骨骺增宽，均提示佝偻病。生化检查还显示甲状旁腺激素（PTH）、1,25 - 二羟维生素D升高，离子钙水平升高。基于这些结果，怀疑为FHH。对患者CaSR基因的序列分析显示外显子7有一个新的错义突变（c.2279T>A），导致成熟CaSR蛋白中出现有害的氨基酸变化（p.I760N），从而确诊FHH。此外，骨骼异常可能与维生素D异常有关，但不限于维生素D异常。青春期PTH水平升高及骨骼快速生长期可能也起了作用。我们的研究表明，在维生素D轻度缺乏的FHH患者中，佝偻病样特征往往表现不典型，且CaSR突变可能在骨骼畸形的发病机制中起部分作用。
