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Clinical and molecular aspects of distal renal tubular acidosis in children

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Pediatric Nephrology Aims and scope Submit manuscript

An Erratum to this article was published on 03 March 2017

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.

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Acknowledgements

Funding for this study was kindly provided by the European Union, FP7 [grant agreement 2012–305608 “European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics)”] and by the British Kidney Patient Association (BKPA).

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK

    Martine T. P. Besouw, Robert Kleta, William G. van’t Hoff & Detlef Bockenhauer

  2. Department of Pediatrics, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany

    Marc Bienias

  3. Great North Children’s Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK

    Patrick Walsh

  4. North East Thames Regional Genetics Service Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Emma Ashton & Lucy Jenkins

  5. Centre for Nephrology, University College London Institute of Child Health, London, UK

    Robert Kleta & Detlef Bockenhauer

Authors
  1. Martine T. P. Besouw
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  2. Marc Bienias
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  3. Patrick Walsh
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  4. Robert Kleta
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  5. William G. van’t Hoff
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  6. Emma Ashton
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  7. Lucy Jenkins
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  8. Detlef Bockenhauer
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Correspondence to Detlef Bockenhauer.

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The authors declare no conflict of interest.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00467-017-3631-6.

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Besouw, M.T.P., Bienias, M., Walsh, P. et al. Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatr Nephrol 32, 987–996 (2017). https://doi.org/10.1007/s00467-016-3573-4

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  • DOI: https://doi.org/10.1007/s00467-016-3573-4

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