ATP6V0A4基因纯合内缺失致远端肾小管酸中毒1例并12年随访分析

Distal tubular acidosis caused by homozygous deletion of ATP6V0A4 gene:a case report and 12 years follow-up analysis

目的分析远端肾小管酸中毒(dRTA)(MIM602722)的临床特点、基因型及预后。方法回顾分析1例dRTA患儿的临床资料并进行文献复习。结果病例为足月剖宫产男婴,出生后34 d体质量不增,血气分析提示阴离子间隙正常的高氯性代谢性酸中毒、低钾血症,碱性尿,肾脏锥体钙化,肾性骨病表现,随访12年,经枸橼酸合剂治疗,体格发育追赶至正常,肾性骨病消失,11岁时出现听力损害、蛋白尿及肾功能损害,基因测序显示患儿ATP6V0A4基因3~5号外显子的纯合缺失,父母亲均存在该基因杂合缺失,此变异为致病性变异,符合常染色体隐性dRTA诊断。结论发病年龄小的dRTA,应尽早干预使患儿获得满意的体格发育结局,基因测序是判定遗传性致病因素的重要手段,可预测远期预后,对遗传咨询具有重要意义,并应长期随访。

Objective To analyze the clinical features,genotypes and prognosis of distal tubular acidosis(dRTA)(MIM602722).Methods The clinical data of a child with dRTA were retrospectively analyzed and a literature review was performed.Results The full-term cesarean section boy did not gain weight on the 34 th day after birth.The blood gas analysis showed the hyperchlorinated acidosis with normal anion gap,hypokalemia,alkaline urine,renal pyramidal calcification,and renal osteopathy.The child was followed up for 12 years.After treatment with citric acid mixture,the child’s physical development caught up to normal,and renal osteopathy disappeared.The child developed hearing impairment,proteinuria and renal impairment at the age of 11.Gene sequencing showed that there was a homozygous deletion in exon 3-5 of APT6V0A4 gene.Both parents had a loss of heterozygosity in this gene.This mutation was pathogenic and consistent with the diagnosis of autosomal recessive dRTA.Conclusion Early intervention should be given to younger patients with dRTA to achieve satisfactory physical development outcome.Gene sequencing is an important means to determine the genetic pathogenic factors,which can predict the long-term prognosis.It is of great significance for genetic counseling and should be followed up for a long time.