HNF1B mutations are associated with a Gitelman-like tubulopathy that develops during childhood

Research output: Contribution to journalArticle

  • External authors:
  • Shazia Adalat
  • W. Hayes
  • W. A. Bryant
  • J. Booth
  • R. Kleta
  • Sandra Subtil
  • R. Clissold
  • K. Colclough
  • S. Ellard
  • D. Bockenhauer


Background: Mutations in the transcription factor HNF1B are the most common inherited cause of renal malformations, yet also associated with renal tubular dysfunction, most prominently magnesium wasting with hypomagnesemia. The presence of hypomagnesemia has been proposed to help select appropriate patients for genetic testing. Yet, in a large cohort, hypomagnesemia was only discriminatory in adult, but not in paediatric patients. We therefore investigated whether hypomagnesemia and other biochemical changes develop with age. Methods: We performed a retrospective analysis of clinical, biochemical and genetic results of paediatric patients with renal malformations tested for HNF1B mutations, separated into 4 age groups. Values were excluded if concurrent estimated glomerular filtration rate (eGFR) was <30 ml/min/1.73m2, or after transplantation. Results: A total of 199 patients underwent HNF1B genetic testing and mutations were identified in 52 (mut+). The eGFRs were comparable between mut+ and mut- in any age group. Although median plasma magnesium concentrations differed significantly between mut+ and mut- patients in all age groups, overt hypomagnesemia was not present until second half of childhood in the mut+ group. There was also a significant difference in median potassium concentrations in late childhood with lower values in the mut+ cohort. Conclusions: The abnormal tubular electrolyte handling associated with HNF1B mutations develops with age and is not restricted to magnesium, but consistent with a more generalized dysfunction of the DCT. The absence of these abnormalities in early childhood should thus not preclude HNF1B mutations from diagnostic considerations.

Bibliographical metadata

Original languageEnglish
JournalKidney International Reports
Publication statusAccepted/In press - 21 May 2019