Gene Variants Associated with Transient Neonatal Diabetes Mellitus in the Very Low Birth Weight Infant

Horm Res Paediatr. 2015;84(4):283-8. doi: 10.1159/000437378. Epub 2015 Aug 28.

Abstract

Background: Transient and permanent neonatal diabetes mellitus (NDM), usually defined as diabetes diagnosed within the first 6 months of life, are rare conditions occurring in 1:90,000-260,000 live births. The origin of NDM is rarely related to type 1 diabetes, but rather to single gene defects.

Methods: Genetic analysis was performed using targeted parallel sequencing including 323 diabetes genes. Data were filtered by a locally developed program.

Results: A very low birth weight neonate born at 28 weeks postmenstrual age developed diabetes 13 days after birth. The patient was treated with continuous subcutaneous insulin infusion. After 1 month, insulin treatment could be stopped. At 18 months of age, the child was normoglycemic and developing normally. Genetic analysis revealed a novel variant (p.Pro190Leu) in HNF4A, which is located in the ligand binding domain of the transcription factor, and the p.Glu23Lys variant in KCNJ11, which is associated with type 2 diabetes.

Conclusion: Here, we describe a novel HNF4A variant associated with transient NDM in a premature infant. We hypothesize that the neonatal phenotype previously described in carriers of HNF4A mutations was modified by the additional variant in KCNJ11 and prematurity.

Publication types

  • Case Reports

MeSH terms

  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / genetics*
  • Female
  • Hepatocyte Nuclear Factor 4 / genetics*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Infant
  • Infant, Newborn
  • Infant, Very Low Birth Weight*
  • Insulin / therapeutic use
  • Mutation*
  • Treatment Outcome

Substances

  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Hypoglycemic Agents
  • Insulin