Department of Endocrinology, Larrey Hospital, CardioMet Institute, University Hospital Centre of Toulouse, Toulouse, France.
Department of Genetics, European Hospital Georges Pompidou, Paris, France.
Clin Endocrinol (Oxf). 2020 Sep;93(3):248-260. doi: 10.1111/cen.14211. Epub 2020 May 14.
Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss-of-function mutations of the calcium-sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.
This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.
Hypercalcaemia was diagnosed at a median age of 53 years [IQR: 38-61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63-2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1-7.1], and the median 24-hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9-4.0]. Osteoporosis (dual X-ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.
This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
家族性低钙血症性高钙血症 1 型（FHH1）与钙敏感受体基因突变的杂合功能丧失有关，是原发性甲状旁腺功能亢进症的主要鉴别诊断。本研究的目的是描述在法国生活的、经基因证实的 FHH1 成年患者的临床特征。
这是一项观察性、回顾性、多中心研究，纳入了 2001 年至 2012 年间在法国 32 个临床科室接受遗传 FHH1 诊断的 77 名成年人。
中位年龄为 53 岁（IQR：38-61）时诊断为高钙血症。58 例患者（19 例患者数据缺失）分别因临床表现、常规分析或家族筛查而做出诊断（分别占 56%、34%和 10%）。11/51 例（22%）患者存在软骨钙质沉着症，8/56 例（14%）患者存在骨骨折，6/55 例（11%）患者存在肾绞痛。中位血清钙为 2.74mmol/L（IQR：2.63-2.86mmol/L），中位血浆甲状旁腺激素水平为 4.9pmol/L（3.1-7.1），24 小时尿钙排泄量中位数为 2.8mmol/24 小时（IQR：1.9-4.0）。6/38 例（16%）患者发现骨质疏松症（双能 X 线吸收法），9/32 例（28%）患者发现肾结石（肾脏超声）。14 例（18%）患者接受甲状旁腺手术；3 例（21%）患者发现甲状旁腺腺瘤，9 例（64%）患者发现甲状旁腺增生。未发现基因型与表型之间存在相关性。
这项大型队列研究表明，33 例（43%）患者的 FHH1 临床特征可能不典型。临床医生应意识到这种罕见的鉴别诊断，以便采取适当的治疗策略。
