A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia.
A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia.
复制标题
DOI：
10.1186/1687-9856-2012-13
复制
发表时间：
2012-05-23
期刊：
影响因子：
--
通讯作者：
Dunbar NS
中科院分区：
文献类型：
--
作者：
Tonyushkina KN;O'Connor S;Dunbar NS
家族性低钙尿性高钙血症(FHH)是一种由于钙敏感受体(CaSR)基因杂合性失活突变导致钙代谢改变而引起的良性疾病。我们报告一例异常严重的新生儿FHH，由一种新的CaSR基因突变引起，表现为围产期骨折和中度高血钙症。一名女婴在2 周大时因疑似非意外创伤(NAT)入院。实验室检查示高钙血症(3.08pmoL/L)，iPTH升高(20.4pmoL/L)，尿钙清除率低(0.0004)。X线片显示多处愈合的干骺端和肋骨骨折，双侧股骨弯曲。股骨畸形和愈合阶段符合产前损伤，而不是非意外损伤(NAT)。治疗开始于胆钙化醇，每天400 IU，到6 周龄时，iPTH水平已降至高值-正常范围。术后3个 月随访X线片显示骨病变明显改善。CaSR基因突变研究表明，第6外显子C.1664处的T>；C核苷酸替换是杂合性的，导致胞外区的氨基酸变化I555T，与错义突变一致。她的母亲没有携带突变，父亲也不清楚。在18个月大的 ，孩子继续有相对甲状旁腺功能亢进症和中度高钙血症，但其他方面是正常的。这名患有宫内骨折和脱矿、中度高血钙症和甲状旁腺功能亢进症的新生儿被发现有一种新的CaSR失活错义突变，在她的母亲中没有检测到。骨损的缓解和甲状旁腺功能亢进症的减少可能归因于这种疾病在婴儿时期的自然演变以及胆钙化醇治疗的缓解效果。
Familial Hypocalciuric Hypercalcemia (FHH) is a generally benign disorder caused by heterozygous inactivating mutations in the Calcium-Sensing Receptor (CaSR) gene resulting in altered calcium metabolism. We report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia. A female infant was admitted at 2 weeks of age for suspected non-accidental trauma (NAT). Laboratory testing revealed hypercalcemia (3.08 mmol/L), elevated iPTH (20.4 pmol/L) and low urinary calcium clearance (0.0004). Radiographs demonstrated multiple healing metaphyseal and rib fractures and bilateral femoral bowing. The femoral deformity and stage of healing were consistent with prenatal injuries rather than non-accidental trauma (NAT). Treatment was initiated with cholecalciferol, 400 IU/day, and by 6 weeks of age, iPTH levels had decreased into the high-normal range. Follow up radiographs demonstrated marked improvement of bone lesions by 3 months. A CaSR gene mutation study showed heterozygosity for a T>C nucleotide substitution at c.1664 in exon 6, resulting in amino acid change I555T in the extracellular domain consistent with a missense mutation. Her mother does not carry the mutation and the father is unknown. At 18 months of age, the child continues to have relative hyperparathyroidism and moderate hypercalcemia but is otherwise normal. This neonate with intrauterine fractures and demineralization, moderate hypercalcemia and hyperparathyroidism was found to have a novel inactivating missense mutation of the CaSR not detected in her mother. Resolution of bone lesions and reduction of hyperparathyroidism was likely attributable to the natural evolution of the disorder in infancy as well as the mitigating effect of cholecalciferol treatment.