目的 探讨儿童原发性远端肾小管酸中毒（dRTA）的临床和基因学特征。方法 回顾分析21例原发性dRTA 患儿的临床资料及基因检测结果。结果 21例患儿中男性12例、女性9例，中位起病年龄9（2~24）月，中位确诊年龄31 （24~54）月。临床特征主要为生长发育迟缓、多饮多尿、喂养困难、乏力、反复泌尿道感染。21例患儿均存在肾髓质钙质沉 积，9例（42.8%）伴有肾脏囊性病，其中3例表现为髓质海绵肾；12例有蛋白尿，其中8例肾小管性蛋白尿、3例混合性蛋白尿、 1例肾小球性蛋白尿，酸中毒纠正后仅1例肾小球性蛋白尿持续存在，余均恢复正常。患儿均予枸橼酸钠、枸橼酸钾溶液治 疗。中位随访时间45（28~61）月。至末次随访时，所有患儿代谢紊乱纠正，1例患儿出现慢性肾功能不全2期。10例患儿行 基因组全外显子测序，6例检测出基因变异，其中3例变异未见报道，分别为ATP6V1B1 c.687 G>A, c.1397C>A（p.P229G, p.S466X）复合杂合变异、ATP6V1B1 c.232 G>A, c.1354 del (p.G78R, p.F452fs）复合杂合变异，及ATP6V0A4 c.1376C>T, c. 1029+5 G>A（p.S 459 P）复合杂合变异。结论 发现3种新发复合杂合变异，扩展了dRTA基因变异谱。基因检测有助 于明确诊断和遗传咨询。

Objective To investigate the clinical characteristics and gene diagnosis of primary distal renal tubular acidosis (dRTA) in children. Methods The clinical data and genetic test results of 21 patients with primary dRTA were retrospectively analyzed. Results Among the 21 children, there were 12 boys and 9 girls. The median onset age was 9 (2~24) months and the median diagnosis age was 31 (24~54) months. The main clinical features were growth retardation, polyuria, feeding difficulties, fatigue and repeated urinary tract infection. All the children had medullary calcareous deposition, and 9 cases (42.8%) had renal cystic disease, including 3 cases with medullary sponge kidney. There were 12 cases of proteinuria, including 8 cases of renal tubular proteinuria, 3 cases of mixed proteinuria and 1 case of glomerular proteinuria. After acidosis was corrected, only one case of glomerular proteinuria persisted, and the rest returned to normal. All children were given sodium citrate and potassium citrate solution orally. The median follow-up time was 45 (28 ~ 61) months. By the time of the last follow-up, all the children's metabolic disorders were corrected and 1 child developed stage 2 chronic renal insufficiency. Total exon sequencing was performed in 10 children, gene variation was detected in 6 children, and no clinical report was found in case 4, 5 and 6. Case 4 was a compound heterozygous mutation of ATP 6 V 1 B 1 c. 687 G> A, c. 1397 C>A (p.P 229 G, p.S 466 X); Case 5 was a compound heterozygous mutation of ATP6V1B1 c.232G >A, c.1354 del (p.G78R, p.F452fs), and case 6 was a compound heterozygous mutation of ATP6V0A4 c.1376C>T, c.1029 + 5G>A (p.S459P). Conclusion In this study, three new compound heterozygous mutations were found, which extended the gene mutation spectrum. Genetic testing is helpful for diagnosis and genetic counseling.