摘要
目的探讨遗传性低镁血症继发低钙血症的临床、生化、影像及TRPM6基因突变特点。方法 2例于2014年至2016年就诊于北京大学第一医院来自不同家系的男童,分别于9岁、1岁2个月时因"癫痫、发育落后"入院,通过临床调查、生化代谢分析、影像进行病因研究,采用全外显子分析明确基因诊断,对TRPM6基因突变进行验证。结果例1出生后3个月起反复抽搐发作,发育落后,9岁起视力下降,智力运动倒退,伴高血压。血镁(0.13~0.15 mmol/L)和血总钙(1.43~2.00 mmol/L)显著降低,伴血钾(1.85~3.25 mmol/L)及甲状旁腺素降低。TRPM6基因检出2个新的无义突变c.2771G>A(p.Trp924Ter)和c.115C>T(p.Gln39Ter)。例2出生后2周出现抽搐发作,发育落后。血镁(0.17~0.35 mmol/L)和血总钙(1.32~1.34 mmol/L)显著降低,甲状旁腺素降低。TRPM6基因检测发现2个新突变c.1239G>A(p.W413X)和c.146G>A(p.C49Y)。2例患儿血清镁、钙显著降低,甲状旁腺素降低,符合遗传性低镁血症继发低钙血症。经大剂量硫酸镁补充治疗后,2例患儿临床症状显著改善,血镁提高,血钙达到正常水平。例1由于脑损伤严重,仍有发育落后。例2已经康复。结论遗传性低镁血症继发低钙血症是一种严重的遗传代谢病,早期诊断、大剂量镁剂治疗预后良好。本研究报道了2例中国患儿,以癫痫、发育落后形式起病,经血液生化及基因分析确诊,并发现了TRPM6 4个新突变。
Objective To investigate the clinical, biochemical and genetic features of hereditary hypomagnesaemia with secondary hypocalcaemia. Methods Two boys came from different Chinese families.They were hospitalized at the Peking University First Hospital between 2014 and 2016 at the age of 9 years and 1 year and 2 months because of epilepsy and psychomotor retardation.Clinical investigation, laboratory examination, and medical imaging were performed for the etiological study.Whole-genome sequencing was used for the genetic analysis of the patients.Mutations of TRPM6 gene were confirmed by means of Sanger sequencing. Results Patient 1 presented with recurrent seizures and psychomotor retardation from the age of 3 months.Vision loss and psychomotor regression were noticed from the age of 9 years, accompanied with hypertension.Serum magnesium and total calcium were significantly decreased to 0.13-0.15 mmol/L and 1.43-2.00 mmol/L, respectively in patient 1.Serum potassium was reduced to 1.85-3.25 mmol/L.Blood parathyroid hormone was also decreased.On the TRPM6 gene of patient 1, 2 novel non-sense mutations, c.2771G>A (p.Trp924Ter) and c. 115C>T (p.Gln39Ter) were identified.Patient 2 presented with seizures and psychomotor retardation at the age of 2 weeks.Both of his serum magnesium (0.17-0.35 mmol/L) and serum total calcium (1.32 - 1.34 mmol/L) were significantly decreased.Blood parathyroid hormone was decreased.Two novel mutations (c.1239G>A, p.W413X and c. 146G>A, p.C49Y) were found in the TRPM6 gene of patient 2.Severe hypomagnesaemia, hypocalcaemia and TRPM6 gene mutations confirmed the diagnosis of hereditary hypomagnesaemia with secondary hypocalcaemia in the 2 patients.After the large-dose supplement of magnesium sulfate, progressive clinical improvements were observed in the 2 patients.However, because of the severe brain damage, patient 1 still had psychomotor retardation.Patient 2 completely recovered. Conclusions Hereditary hypomagnesaemia with secondary hypocalcaemia is a severe inherited metabolic disease.Ear
作者
张尧
刘怡
康路路
李东晓
吴晔
杨艳玲
张月华
Zhang Yao;Liu Yi;Kang Lulu;Li Dongxiao;Wu Ye;Yang Yanling;Zhang Yuehua(Department of Pediatrics, Peking University First Hospital, Beijing 100034, China)
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2019年第8期582-586,共5页
Chinese Journal of Applied Clinical Pediatrics
基金
国家自然科学基金(81471097)
国家重点研发计划(2017YFC1001704).
