Madhavan Parvathy, Van Do Thi Hong, Bale Allen, Majumdar Sachin
AACE Clin Case Rep. 2019 Mar 13;5(4):e226-e229. doi: 10.4158/ACCR-2018-0236. eCollection 2019 Jul-Aug.
Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by elevated serum calcium with relatively low urinary calcium excretion. It typically results from an altered set point in calcium homeostasis originating from mutations in the calcium-sensing receptor (), , or genes, which encode for the calcium-sensing receptor (CaSR), adaptor-related protein complex 2, and G-protein alpha-11 subunit, respectively. Despite numerous reports of novel variants in these genes associated with FHH, new variants continue to be discovered.
We describe a 20-year-old man with a family history of hypercalcemia who had clinical findings compatible with FHH and no evidence of multiple endocrine neoplasia who underwent gene sequencing for evaluation of hypercalcemia. Parathyroid gland single-photon emission computerized tomography scan was normal.
gene sequencing revealed a previously unreported heterozygous intronic variant at position 1608+3A>G (chromosome 3: 121994892) resulting in a 77-residue deletion. His mother has a history of bipolar disorder and hyperparathyroidism with an adenoma found on imaging, yet our patient had no evidence of adenoma and therefore no surgical intervention was recommended. Given that CaSR plays a role in parathyroid growth, some variants in may ultimately lead to parathyroid hypertrophy and be mistaken for primary hyperparathyroidism.
Long-term clinical follow up will be helpful in understanding the ultimate effects of specific mutations on parathyroid growth or progression to significant hypercalcemia.
家族性低钙血症性高钙血症（FHH）被认为是一种相对良性的病症，其特征是血清钙升高而尿钙排泄相对较低。它通常是由于钙稳态设定点改变所致，源于钙敏感受体（CaSR）、 adaptor相关蛋白复合体2（AP2S1）或G蛋白α-11亚基（GNA11）基因的突变，这些基因分别编码钙敏感受体（CaSR）、 adaptor相关蛋白复合体2和G蛋白α-11亚基。尽管有许多关于这些与FHH相关基因的新变异的报道，但新的变异仍在不断被发现。
我们描述了一名有高钙血症家族史的20岁男性，其临床表现与FHH相符，且无多发性内分泌肿瘤的证据，为评估高钙血症而接受了CaSR基因测序。甲状旁腺单光子发射计算机断层扫描正常。
CaSR基因测序显示在位置1608 + 3A>G（染色体3：121994892）处有一个先前未报道的杂合内含子变异，导致77个氨基酸残基缺失。他的母亲有双相情感障碍和甲状旁腺功能亢进病史，影像学检查发现有腺瘤，但我们的患者没有腺瘤证据，因此不建议进行手术干预。鉴于CaSR在甲状旁腺生长中起作用，CaSR基因的一些变异最终可能导致甲状旁腺肥大，并被误诊为原发性甲状旁腺功能亢进。
长期临床随访将有助于了解特定CaSR突变对甲状旁腺生长或进展为严重高钙血症的最终影响。
