多脏器型假性醛固酮减少症Ⅰ型1例并文献复习

摘要

目的 报告1例SCNN1A基因杂合突变所致的多脏器型假性醛固酮减少症Ⅰ型(PHA Ⅰ),为PHA Ⅰ患儿的早期诊断、治疗等提供依据.方法 总结患儿的临床表型、实验室检查、基因测序结果和诊治经过,并对多脏器型PHA Ⅰ行文献复习.结果 患儿男,17d,因“发现电解质紊乱6d”入院,主要表现为低钠血症、高钾血症和代谢性酸中毒.经补钠、氢化可的松和胰岛素等治疗效果不理想.核心家系全外显子检测发现SCNN1A复合杂合变异c.1439+ 1G＞C和c.104delC(p.P35LfsTer14).c.1439+1G＞C源于患儿父亲,是人类基因突变数据库(HGMD)已报道的多脏器型PHA Ⅰ型的致病突变;c.104delC(p.P35LfsTer14)源于患儿母亲,系新发现的突变.明确诊断多脏器型PHA Ⅰ后拟予口服降钾树脂治疗,患儿家属放弃治疗,出院后第4d患儿死亡.检索Pubmed、中国期刊全文数据库、万方数据库、中文科技期刊数据库和中国生物医学文献数据库,检索时间从建库至2017年9月4日,14篇文献(13篇英文,1篇中文)共报告33例多脏器型PHA Ⅰ型患儿,与本文1例合并后共34例.34例均有肾脏表现.除3例SCNN1A纯合突变及1例SCNN1G杂合突变在病程及随访中未提及肾外表现外,余病例均报道累及肾外其他系统,其中脱水样改变和累及呼吸道最常见,发育迟缓和消化道次之.4例死于高血钾所致心脏骤停,均为SCNN1A突变,除本文报告的1例为杂合突变外均为纯合突变.结论 顽固性高钾血症、低钠血症和代谢性酸中毒需考虑PHA,基因测序可协助诊断.%Objective To report a neonate diagnosed as multi-system pseudohypoaldosteronism type Ⅰ (PHA Ⅰ) caused by SCNN1A gene heterozygous mutation,provide the basis for early diagnosis and clinical decision-making of PHA Ⅰ.Methods Analysis was performed on clinical manifestation,imageological examination,parental sanger test and treatment process of a patient carrying a pair of compound heterozygous mutaions of SCNN1A,and literatures about clinical features of PHA Ⅰ.Results A 17-day-old boy presented with electrolyte disturbances including hyponatremia,hyperkalemia,and metabolic acidosis for 6 days.The effects of sodium supplement,hydrocortisone and insulin were not satisfactory.A pair of compound heterozygous mutations of SCNN1A was found by WES.c.1439+1G＞C was from father and had reported as a pathogenic mutation of PHA Ⅰ by HGMD,while c.104delC (p.P35LfsTer14) was a novel deletion mutation from mother.The patient was finally diagnosed as multi-system PHA Ⅰ.The children's parents gave up to treat with oral potassiun lowering resin,and the children died the fourth days after discharge.Databases were searched including PubMed,CNKI,Wan Fang Database,China Science and Technology Database and CBMdisc,which described the muhi-system PHA Ⅰ from database-buiding time to September 4,2017.A total of 14 articles (13 English,1 Chinese) were screened out.Renal manifestations were found in all 34 cases.Except 3 cases of SCNN1A and 1 case of SCNN1G did not mention multi-system manifestations,the remaining cases reported dehydration and respiratory changes were the most commom manifestations,followed by stunted growth and digestive manifestations.4 cases died of cardiac arrest caused by hyperkalemia,all of them were SCNN1A mutations,except our study with heterozygous mutation the rest were homozygous mutations.Conclusion Pseudohypoaldosteronism should be considered when lasted intractable hyperkalemia,hyponatremia and metabolic acidosis happened.Neonatal gene sequencing can help diagnosis.