title: Familial autosomal recessive renal tubular acidosis: importance of early diagnosis.
abstract: OBJECTIVE
  Untreated renal tubular acidosis (RTA) can result in severe complications. We reviewed the clinical features of patients with mutations in two genes causing RTA and evaluated their developmental expression assuming that timing, symptom severity and complications may be related to its occurrence.
  
  
  METHODS
  Clinical data from 16 patients with RTA due to mutations in either ATP6V1B1 or CAII were retrospectively reviewed. Both genes' localization and expression pattern in the developing human kidney were analyzed by real-time polymerase chain reaction and immunostaining.
  
  
  RESULTS
  RTA-presenting symptoms were non-specific. Patients with mutations in ATP6V1B1 had earlier presentation (4.9 vs. 11 months, p < 0.041) and longer time to diagnosis than patients with CAII mutations (5.8 vs. 57 months, p < 0.01). Patients with ATP6V1B1 mutations were more likely to develop chronic kidney disease than those with CAII mutations (follow-up GFR values: 89 vs. 110 ml/min/1.73 m2, respectively, p < 0.017), probably secondary to nephrocalcinosis. Both ATP6V1B1 and CAII were expressed early during human nephrogenesis, with relatively higher transcript levels of ATP6V1B1.
  
  
  CONCLUSIONS
  There is considerable delay in establishing a diagnosis of both types of RTA, supporting the need for earlier biochemical investigation. RTA due to ATP6V1B1 mutations is associated with mild progressive loss of kidney function.
authors.affiliation: Department of Pediatrics, Talpiot Medical Leadership Program, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Vivante
authors.forename: Danny
authors.initials: D
authors.lastname: Lotan
authors.forename: Naomi
authors.initials: N
authors.lastname: Pode-Shakked
authors.forename: Daniel
authors.initials: D
authors.lastname: Landau
authors.forename: Peter
authors.initials: P
authors.lastname: Svec
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Ishwar
authors.initials: I
authors.lastname: Verma
authors.forename: Abdulsalam
authors.initials: A
authors.lastname: Abu-Libdeh
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dekel
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
mesh_terms: D000141:Acidosis, Renal Tubular / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D000293:Adolescent; D024403:Carbonic Anhydrase III / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D042241:Early Diagnosis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000150:complications / Q000235:genetics; D010375:Pedigree; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*; D055815:Young Adult
chemical_list: C509766:ATP6V1B1 protein, human; D025262:Vacuolar Proton-Translocating ATPases; D024403:Carbonic Anhydrase III