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Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis.
Kidney Blood Press Res 2018; 43(2):513-521KB

Abstract

BACKGROUND/AIMS

Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA.

METHODS

A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes.

RESULTS

Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype-phenotype correlation.

CONCLUSIONS

SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA.

Authors+Show Affiliations

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea.Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea.Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea.Department of Pediatrics, Severance Children's Hospital, Yonsei University, Seoul, Republic of Korea.Department of Pediatrics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.Department of Pediatrics, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea.Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Republic of Korea.Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Republic of Korea. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29627839

Citation

Park, Eujin, et al. "Genotype-Phenotype Analysis in Pediatric Patients With Distal Renal Tubular Acidosis." Kidney & Blood Pressure Research, vol. 43, no. 2, 2018, pp. 513-521.
Park E, Cho MH, Hyun HS, et al. Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis. Kidney Blood Press Res. 2018;43(2):513-521.
Park, E., Cho, M. H., Hyun, H. S., Shin, J. I., Lee, J. H., Park, Y. S., ... Cheong, H. I. (2018). Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis. Kidney & Blood Pressure Research, 43(2), pp. 513-521. doi:10.1159/000488698.
Park E, et al. Genotype-Phenotype Analysis in Pediatric Patients With Distal Renal Tubular Acidosis. Kidney Blood Press Res. 2018;43(2):513-521. PubMed PMID: 29627839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis. AU - Park,Eujin, AU - Cho,Myung Hyun, AU - Hyun,Hye Sun, AU - Shin,Jae Il, AU - Lee,Joo Hoon, AU - Park,Young Seo, AU - Choi,Hyun Jin, AU - Kang,Hee Gyung, AU - Cheong,Hae Il, Y1 - 2018/03/29/ PY - 2018/01/19/received PY - 2018/03/23/accepted PY - 2018/4/9/pubmed PY - 2018/10/30/medline PY - 2018/4/9/entrez KW - Chronic kidney disease KW - Distal renal tubular acidosis KW - Growth retardation KW - Mutations KW - Nephrocalcinosis KW - Sensorineural hearing loss SP - 513 EP - 521 JF - Kidney & blood pressure research JO - Kidney Blood Press. Res. VL - 43 IS - 2 N2 - BACKGROUND/AIMS: Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. METHODS: A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. RESULTS: Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype-phenotype correlation. CONCLUSIONS: SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA. SN - 1423-0143 UR - https://www.unboundmedicine.com/medline/citation/29627839/Genotype_Phenotype_Analysis_in_Pediatric_Patients_with_Distal_Renal_Tubular_Acidosis_ L2 - https://www.karger.com?DOI=10.1159/000488698 DB - PRIME DP - Unbound Medicine ER -