RESUMO
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.
