New-onset diabetes after renal transplantation in a patient with a novel HNF1B mutation

Pediatr Transplant. 2016 May;20(3):467-71. doi: 10.1111/petr.12690. Epub 2016 Feb 21.

Abstract

CAKUT are the most frequent causes of ESRD in children. Mutations in the gene encoding HNF1B, a transcription factor involved in organ development and maintenance, cause a multisystem disorder that includes CAKUT, diabetes, and liver dysfunction. Here, we describe the case of a patient with renal hypodysplasia who developed NODAT presenting with liver dysfunction. The NODAT was initially thought to be steroid and FK related. However, based on the patient's clinical features, including renal hypodysplasia and recurrent elevations of transaminase, screening for an HNF1B mutation was performed. Direct sequencing identified a novel splicing mutation of HNF1B, designated c.344 + 2T>C. Because CAKUT is the leading cause of ESRD in children and HNF1B mutations can cause both renal hypodysplasia and diabetes, HNF1B mutations may account for a portion of the cases of NODAT in pediatric patients who have undergone kidney transplantation. NODAT is a serious and major complication of solid organ transplantation and is associated with reduced graft survival. Therefore, for the appropriate management of kidney transplantation, screening for HNF1B mutations should be considered in pediatric patients with transplants caused by CAKUT who develop NODAT and show extra-renal symptoms.

Keywords: HNF1B; NODAT; complications; pediatric kidney transplantation.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Alternative Splicing
  • Child
  • Child, Preschool
  • Diabetes Mellitus / genetics*
  • Female
  • Graft Survival
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Kidney / physiopathology*
  • Kidney Diseases / physiopathology
  • Kidney Transplantation*
  • Male
  • Mutation*
  • Pediatrics / methods
  • Renal Insufficiency / complications
  • Renal Insufficiency / genetics
  • Renal Insufficiency / surgery*
  • Sequence Analysis, DNA
  • Steroids / therapeutic use
  • Transaminases / blood
  • Urogenital Abnormalities / complications
  • Urogenital Abnormalities / genetics
  • Vesico-Ureteral Reflux / complications
  • Vesico-Ureteral Reflux / genetics

Substances

  • HNF1B protein, human
  • Steroids
  • Hepatocyte Nuclear Factor 1-beta
  • Transaminases

Supplementary concepts

  • Cakut