假性醛固酮减少症1型6例患儿的临床特征及基因结果并文献复习

Clinical features and genetic results of 6 cases with pseudohypoaldosteronism type 1 and literature review

目的总结假性醛固酮减少症1型(PHA1)不同类型的临床特征、诊治经过及预后并进行文献复习,提高对该病的认识,减少漏诊误诊。方法收集2015年1月至2018年12月上海市儿童医院收治的6例以失盐为主要表现的患儿,完善相关辅助检查及基因检测诊断PHA1并进行分类,同时收集了患儿的诊治经过及随访预后。结果6例患儿均有不同程度失盐、脱水及感染表现。根据检查结果3例患儿存在泌尿系统畸形,诊断为继发性PHA1,2例患儿进行了基因检测发现SCNN1A基因的内含子区域都存在c.1439+1G>C和c.875+1G>A两个杂合突变,并进行了核心家系分析,根据美国医学遗传学和基因组学会(ACMG)指南诊断为多脏器型PHA1。另1例由于家长因素未能行基因检测协助分型,根据临床诊治经过临床诊断肾型PHA1。结论PHA1是婴儿失盐综合征的少见病因,肾型和继发性PHA1患儿予补钠及解除继发因素后可很快恢复;而多脏器型PHA1失盐表现严重,易发生致死性的心律失常,死亡率高。临床容易误诊漏诊,辅助检查及基因检测有助于明确诊断并进行分类,有助于个体化治疗。

Objective To summarize clinical features,diagnosis,treatment,and follow-up of children with pseudohypoaldosteronism type 1(PHA1)and review relevant literatures to improve the understanding of the disease and reduce misdiagnosis.Methods Six children with the main performance of salt losing treated in the Shanghai Children′s Hospital from January 2015 to December 2018,who were diagnosed as PHA1 after relevant auxiliary examinations and genetic tests.They were classified and analyzed for their treatment courses and follow-up prognosis.Results Six children with PHA1 had varying degrees of salt losing,dehydration and infection.After the examination,3 cases with urinary system malformations were diagnosed as secondary PHA1.Genetic testing of 2 cases revealed 2 hete-rozygous mutations c.1439+1G>C and c.875+1G>A in the intron region of the SCNN1A gene,and they were diagnosed as multiple target organ defect/systemic PHA1 according to American College of Medical Genetics and Genomics(ACMG)guidelines.The other case failed to be examined by genetic testing due to the refusal of parents,and was finally diagnosed as renal PHA1 according to clinical diagnosis and treatment.Conclusions PHA1 is a rare cause of infant salt-losing syndrome,renal and secondary PHA1 children can recover quickly after sodium supplementation and the secondary factors are removed;while multiple target organ defect/systemic PHA1 has severe clinical manifestations,electrolyte imbalance is not easy to correct,and fatal arrhythmia is prone to occur,the mortality rate is high.It is easy to be misdiagnosed in clinical practice.Auxiliary examination and genetic testing can help to diagnose and classify PHA1,as well as individualized treatment.