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Clinical and molecular aspects of distal renal tubular acidosis in children.
Pediatr Nephrol 2017; 32(6):987-996PN

Abstract

BACKGROUND

Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced urinary acidification by the α-intercalated cells in the collecting duct and can be caused by mutations in genes that encode subunits of the vacuolar H+-ATPase (ATP6V1B1, ATP6V0A4) or the anion exchanger 1 (SLC4A1). Treatment with alkali is the mainstay of therapy.

METHODS

This study is an analysis of clinical data from a long-term follow-up of 24 children with dRTA in a single centre, including a genetic analysis.

RESULTS

Of the 24 children included in the study, genetic diagnosis was confirmed in 19 patients, with six children having mutations in ATP6V1B1, ten in ATP6V0A4 and three in SLC4A1; molecular diagnosis was not available for five children. Five novel mutations were detected (2 in ATP6V1B1 and 3 in ATP6V0A4). Two-thirds of patients presented with features of proximal tubular dysfunction leading to an erroneous diagnosis of renal Fanconi syndrome. The proximal tubulopathy disappeared after resolution of acidosis, indicating the importance of following proximal tubular function to establish the correct diagnosis. Growth retardation with a height below -2 standard deviation score was found in ten patients at presentation, but persisted in only three of these children once established on alkali treatment. Sensorineural hearing loss was found in five of the six patients with an ATP6V1B1 mutation. Only one patient with an ATP6V0A4 mutation had sensorineural hearing loss during childhood. Nine children developed medullary cysts, but without apparent clinical consequences. Cyst development in this cohort was not correlated with age at therapy onset, molecular diagnosis, growth parameters or renal function.

CONCLUSION

In general, the prognosis of dRTA is good in children treated with alkali.

Authors+Show Affiliations

Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.Department of Pediatrics, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.Great North Children's Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK.Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK. Centre for Nephrology, University College London Institute of Child Health, London, UK.Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.North East Thames Regional Genetics Service Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.North East Thames Regional Genetics Service Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK. detlef.bockenhauer@gosh.nhs.uk. Centre for Nephrology, University College London Institute of Child Health, London, UK. detlef.bockenhauer@gosh.nhs.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28188436

Citation

Besouw, Martine T P., et al. "Clinical and Molecular Aspects of Distal Renal Tubular Acidosis in Children." Pediatric Nephrology (Berlin, Germany), vol. 32, no. 6, 2017, pp. 987-996.
Besouw MTP, Bienias M, Walsh P, et al. Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatr Nephrol. 2017;32(6):987-996.
Besouw, M. T. P., Bienias, M., Walsh, P., Kleta, R., Van't Hoff, W. G., Ashton, E., ... Bockenhauer, D. (2017). Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatric Nephrology (Berlin, Germany), 32(6), pp. 987-996. doi:10.1007/s00467-016-3573-4.
Besouw MTP, et al. Clinical and Molecular Aspects of Distal Renal Tubular Acidosis in Children. Pediatr Nephrol. 2017;32(6):987-996. PubMed PMID: 28188436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and molecular aspects of distal renal tubular acidosis in children. AU - Besouw,Martine T P, AU - Bienias,Marc, AU - Walsh,Patrick, AU - Kleta,Robert, AU - Van't Hoff,William G, AU - Ashton,Emma, AU - Jenkins,Lucy, AU - Bockenhauer,Detlef, Y1 - 2017/02/10/ PY - 2016/11/01/received PY - 2016/12/19/accepted PY - 2016/12/16/revised PY - 2017/2/12/pubmed PY - 2017/12/30/medline PY - 2017/2/12/entrez KW - Distal renal tubular acidosis KW - Gene mutation KW - Hypokalaemia KW - Medullary cysts KW - Metabolic acidosis KW - Nephrocalcinosis SP - 987 EP - 996 JF - Pediatric nephrology (Berlin, Germany) JO - Pediatr. Nephrol. VL - 32 IS - 6 N2 - BACKGROUND: Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced urinary acidification by the α-intercalated cells in the collecting duct and can be caused by mutations in genes that encode subunits of the vacuolar H+-ATPase (ATP6V1B1, ATP6V0A4) or the anion exchanger 1 (SLC4A1). Treatment with alkali is the mainstay of therapy. METHODS: This study is an analysis of clinical data from a long-term follow-up of 24 children with dRTA in a single centre, including a genetic analysis. RESULTS: Of the 24 children included in the study, genetic diagnosis was confirmed in 19 patients, with six children having mutations in ATP6V1B1, ten in ATP6V0A4 and three in SLC4A1; molecular diagnosis was not available for five children. Five novel mutations were detected (2 in ATP6V1B1 and 3 in ATP6V0A4). Two-thirds of patients presented with features of proximal tubular dysfunction leading to an erroneous diagnosis of renal Fanconi syndrome. The proximal tubulopathy disappeared after resolution of acidosis, indicating the importance of following proximal tubular function to establish the correct diagnosis. Growth retardation with a height below -2 standard deviation score was found in ten patients at presentation, but persisted in only three of these children once established on alkali treatment. Sensorineural hearing loss was found in five of the six patients with an ATP6V1B1 mutation. Only one patient with an ATP6V0A4 mutation had sensorineural hearing loss during childhood. Nine children developed medullary cysts, but without apparent clinical consequences. Cyst development in this cohort was not correlated with age at therapy onset, molecular diagnosis, growth parameters or renal function. CONCLUSION: In general, the prognosis of dRTA is good in children treated with alkali. SN - 1432-198X UR - https://www.unboundmedicine.com/medline/citation/28188436/Clinical_and_molecular_aspects_of_distal_renal_tubular_acidosis_in_children_ L2 - https://dx.doi.org/10.1007/s00467-016-3573-4 DB - PRIME DP - Unbound Medicine ER -