摘要
Abstract
Objective To investigate the clinical charateristics and treatment outcome of children with primary distal tubular acidosis(dRTA),analyze the difference among children with different gene phenotypes,and to improve the understanding of primary dRTA in children.Methods From April 2011 to November 2022,19 patients diagnosed with primary dRTA were included.Clinical and laboratory characteristics were summarized and compared among genotype.Outcome factors were also analyzed.Results There were 19 patients(8 males and 11 females).The age of onset ranged from 10 days to 4 years.The last follow-up age was 8 months to 17 years and one month.Growth retardation was the most common clinical symptom.Height or weight below-2SD accounted for 78.94％.All patients had hypokalemia,hyperchloremic metabolic acidosis,alkaline urine,increased urine calcium and renal medullary calcinosis.Twenty mutations of SCL4A1,ATP6V0A4 and ATP6V1B1 gene were found in the 19 patients,and 9 of them were novel mutations.The proportion of patients with SLC4A1 recessive inheritance and SLC4A1 dominant inheritance,ATP6V0A4 and ATP6VB1 inheritance was 31.58％,15.79％,36.84％and 15.79％,respectively.The onset age of patients with SLC4A1 mutations was significantly higher than patients with ATP6V0A4 and ATP6VB1 mutations(P＜0.001).Bicarbonate level of SLC4A1 recessiveinherited patients was significantly lower than others(P=0.01).Combination rate of bone abnormalities:in SLC4A1 dominant inherited patients it was 66.67％,in SLC4A1 recessive inherited patients it was 100％,in ATP6V1B1 group in was 33.33％,and in ATP6V0A4 group it was 0;there was statistical difference among the four groups(P＜0.001).Three patients had sensorineural hearing loss(1 of ATP6V0A4,2 of ATP6V1B1).The proportion of patients with ATP6V0A4 mutations combined with sensorineural hearing loss was significantly lower than that reported abroad.After treatment with citric acid preparation,68.42％of the patients had a height and weight of more than-2SD,which were significantly positively correlated with the time of treatment(related coefficients 0.627),but had no significant relationship with genotype.After treatment,blood potassium remained normal,and 71.43％of patients'blood bicarbonate remained normal.Only one patient had eGFR lower than 90ml/min/1.73m2 after 8 years of treatment.There was no significant genotypic difference in treatment outcome.In addition,the allele frequency of SLC4A1 c.2102G＞A(p.G701D)was 83.33％,which was a hot spot mutation in SLC4A1 recessive patients.All patients carrying this mutation in this study came from southern China.ATP6V0A4 c.580C＞T(p.R194X)mutation gene frequency was 28.57％,which was considered to be a hot mutation in Chinese population,and all patients with this mutation came from North China.Conclusion Different genotypes of primary dRTA have different phenotypes.Patients with SLC4A1 mutation have a late onset age and more bone involvement.Patients with SLC4A1 recessive mutations often suffer from severe acidosis.After appropriate treatment,the condition of patients with all genotypes improved,and prognosis in childhood is good without end point.This study reveals 9 new mutations,which have enriched the human gene mutation database.The ATP6V0A4 c.580C＞T(p.R194X)mutation and SLC4A1 c.2102G＞A(p.G701D)are consistent with the hot spot mutation of Chinese population,and there are hot spot regional differences.There is no end event under the current follow-up age and current treatment.关键词
原发性远端肾小管酸中毒/基因/佝偻病/生长迟缓Key words
distal renal tubular acidosis/gene/rickets/growth retardation分类
医药卫生
