title: Clinical and molecular aspects of distal renal tubular acidosis in children.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  In general, the prognosis of dRTA is good in children treated with alkali.
authors.affiliation: Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.
authors.forename: Martine T P
authors.initials: MTP
authors.lastname: Besouw
authors.affiliation: Department of Pediatrics, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Bienias
authors.affiliation: Great North Children's Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Walsh
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.affiliation: Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.
authors.forename: William G
authors.initials: WG
authors.lastname: Van't Hoff
authors.affiliation: North East Thames Regional Genetics Service Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Ashton
authors.affiliation: North East Thames Regional Genetics Service Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Jenkins
authors.affiliation: 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.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
mesh_terms: D000141:Acidosis, Renal Tubular / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D000468:Alkalies / Q000627:therapeutic use*; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D003560:Cysts / Q000453:epidemiology / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D005919:Glomerular Filtration Rate; D006130:Growth Disorders / Q000453:epidemiology* / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007679:Kidney Medulla / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009154:Mutation; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
chemical_list: C509766:ATP6V1B1 protein, human; D000468:Alkalies; D001457:Anion Exchange Protein 1, Erythrocyte; C454201:SLC4A1 protein, human; C490181:ATP6V0A4 protein, human; D025262:Vacuolar Proton-Translocating ATPases
keywords: Distal renal tubular acidosis; Gene mutation; Hypokalaemia; Medullary cysts; Metabolic acidosis; Nephrocalcinosis