一个假性醛固酮减少症Ⅱ型家系临床和基因分析并文献复习

A pedigree of pseudohypoaldosteronism typeⅡand review of literature

收集1个假性醛固酮减少症Ⅱ型(pseudohypoaldosteronism type II,PHA2)家系患者临床资料、化验检查及基因突变结果。先证者,1岁7个月,发现血钾6.69 mmol/L(参考范围3.5~5.3 mmol/L,下同)、血压110/68 mmHg(<106/61 mmHg,1 mmHg=0.133 kPa)、血氯111.5 mmol/L(99~110 mmol/L)、血HCO3-17.1 mmol/L(22~29 mmol/L)、估算的肾小球滤过率128.5 mL·min^(-1)·(1.73 m^(2))^(-1)[>90 mL·min^(-1)·(1.73 m^(2))^(-1)]、血肾素浓度0.30μIU/mL(4.2~45.6μIU/mL);其母亲、外祖父也有肾功能正常情况下高血钾、高血压、高血氯、代谢性酸中毒、低肾素。3例患者基因结果显示,无赖氨酸激酶4(WNK4)基因第7号外显子存在1个杂合错义变异(c.1685A>G,p.E562G);氢氯噻嗪治疗均有效。通过文献复习,将本文E562G家系与其他WNK4变异型进行了比较,提示WNK4突变型的临床表型异质性。对于不明原因的高钾血症,尤其合并高血压,要警惕PHA2,尽早进行基因筛查,避免PHA2漏诊误诊。

The clinical data,laboratory test,and gene mutations were collected from a family with pseudohypoaldosteronism type II(PHA2).The proband,aged 1 year and 7 months,presented with hyperkalemia(6.69 mmol/L;reference range 3.5-5.3 mmol/L),blood pressure of 110/68 mmHg(normal<106/61 mmHg,1 mmHg=0.133 kPa),blood chloride of 111.5 mmol/L(reference 99-110 mmol/L),blood HCO 3-of 17.1 mmol/L(reference 22-29 mmol/L),estimated glomerular filtration rate of 128.5 mL·min^(-1)·(1.73 m^(2))^(-1)[>90 mL·min^(-1)·(1.73 m^(2))^(-1)],and blood renin concentration of 0.30μIU/mL(reference 4.2-45.6μIU/mL).The mother and maternal grandfather also exhibited normal renal function with hyperkalemia,hypertension,hyperchloremia,metabolic acidosis,and low renin.Genetic testing revealed a heterozygous missense mutation(c.1685A>G,p.E562G)in exon 7 of the no-lysine kinase 4(WNK4)gene.Treatment with hydrochlorothiazide was effective.Literature review comparing this E562G pedigree with other WNK4 variants suggested clinical heterogeneity of WNK4 mutations.For unexplained hyperkalemia,especially with concurrent hypertension,PHA2 should be considered early for genetic screening to prevent misdiagnosis or delayed diagnosis.