Genotype-phenotype analysis and prognosis in children with primary distal renal tubular acidosis
10.3760/cma.j.cn112140-20211212-01036
- VernacularTitle:基于基因型的儿童原发性远端肾小管酸中毒临床特征及预后比较
- Author:
Yaru JIANG
1
;
Mo WANG
;
Junli WAN
;
Gaofu ZHANG
;
Haiping YANG
;
Qiu LI
Author Information
1. 重庆医科大学附属儿童医院肾内科 国家儿童健康与疾病临床医学研究中心 儿童发育疾病研究教育部重点实验室 儿科学重庆市重点实验室，重庆 400014
- Keywords:
Acidosis, renal tubular;
Genotype;
Prognosis
- From:
Chinese Journal of Pediatrics
2022;60(7):700-705
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The purpose of this study was to investigate the relationship between genotypes and clinical phenotypes of primary distal renal tubular acidosis (dRTA) in children.Methods:Clinical information, genetic testing information and follow-up data (until March 2021) of children with dRTA from Children′s Hospital of Chongqing Medical University (from January 2010 to December 2020) were analyzed retrospectively. According to different pathogenic genes, patients were divided into SLC4A1 gene and ATP6V0A4+ATP6V1B1 gene groups. Age at onset, clinical manifestations and laboratory findings were compared. Self-comparisons of height standard deviation score (HtSDS), weight standard deviation score (WtSDS), blood pH and serum potassium before and after treatment were tested. T-test, Fisher′s exact test and rank sum test were used to analyze among groups. Results:Among 27 children with dRTA (16 boys and 11 girls), the age of onset was 33.4 (10.0, 36.0) months.There were 22 patients (81%) with SLC4A1 gene variation, 3 patients (11%) with ATP6V1B1 gene variation and 2 patients (8%) with ATP6V0A4 gene variation. Totally 22 patients (81%) with renal calcium deposition, 19 patients (70%) hypokalemia, 18 patients (67%) short stature, 16 patients (59%) malnutrition, 16 patients (59%) rickets, and 15 patients (56%) polydipsia and polyuria. Noteworthily, the genotyping results indicated that the age at onset in SLC4A1 gene group was older than that in ATP6V0A4+ATP6V1B1 gene group, with a statistically significant difference (27.3 (12.0, 36.0) vs. 8.2 (2.5, 15.0) months, H=6.33, P=0.012). However, there were no significant differences in clinical manifestations or laboratory test results (all P>0.05). Furthermore, the course of disease was 3.9 (1.3, 6.0) years and the follow-up period was 3.1 (1.0, 4.5) years in 27 patients. In addition, there were no significant differences in recovery rate of clinical manifestations and last laboratory findings between SLC4A1 gene group and ATP6V0A4+ATP6V1B1 gene group (all P>0.05). HtSDS and WtSDS of those patients significantly increased after treatment (-3.2±1.9 vs. -2.1±1.1, -2.5±1.5 vs. 0±1.9, t=-2.94, -5.44, both P<0.01). Serum K + and blood pH were restored eventually ((3.2±0.5) vs. (4.0±0.5) mmol/L, 7.27±0.07 vs. 7.37±0.07, t=-4.92, -5.25, both P<0.01). Totally 14 patients had normalized serum potassium, 12 patients had normalized blood pH, but only 4 patients had normalized serum bicarbonate concentration and normal base excess. Conclusions:The age of onset of patients who had SLC4A1 gene mutation was older than that of patients with ATP6V0A4 gene and ATP6V1B1 gene mutations. However, there was no obvious correlation between the condition and prognosis of the dRTA patients and pathogenic genes. Early diagnosis, early treatment, regular follow-up and timely adjustment of the dosage of medication can significantly improve the prognosis of dRTA in children. Serum bicarbonate concentration and actual base excess might not be the necessory indicators to assess clinical recovery.
