Background Neonatal diabetes is a monogenic type of diabetes mellitus occurs before the age of 6 months and can be transient or permanent. We present a case of neonatal diabetes with positive mutations in KCNJ11 and HNF4A gene. There is no such case described in literature before. This study aims to highlight the importance of the genetic mutations associated with neonatal diabetes.

Case Presentation Previously healthy, 4-month-old male infant born FT with B Wt of 3.0 kg presented with vomiting. Initial investigation showed BG of 368 mg/dL, bicarb of 8.9 and PH of 7.0. HbA1c 13.4%. Upon DKA was resolved, he was transitioned to SQ insulin and later to insulin pump (omnipod) by 1st week post diagnosis. He had negative T1DM antibodies. At 8 month of life, genetic testing was done. It reports mutation in

1. KCNJ11; KCNJ11-related neonatal diabetes, Autosomal Dominant. c.149 G>A p.(R50Q) Heterozygous AND

2. HNF4A; HNF4A-related disorder, Autosomal Dominant. c.-79 C>T Heterozygous

He was started on Glyburide (Glibenclamide) ~0.2 mg/kg/day in two divided doses. By 3rd day, his basal insulin dose were down to half. By 1st week, he was off insulin with stable blood glucose. His current dose is ~0.03 mg/kg/day at 20 month of age with HbA1c of 5.9%. He gets mild hypoglycemic ~2 hr (in 60’s) after the medication dose. Medication effect lasts for ~11 hours. There is no food restriction.

Discussion Mutations in the gene KCNJ11 is among the most common causes of permanent neonatal DM. Mutations in the HNF4A gene can lead to a condition called maturity-onset diabetes of the young type 1 (MODY1), which is a monogenic form of diabetes characterized by early-onset diabetes often before the age of 25. Our case present rare incidence of having both mutations together. As expected, he responded well to Sulfonylureas which closes the KATP channel and initiate insulin secretion which was affected by KCNJ11 mutation. However, the current requirement of Glyburide dose is much lower than expected. It’s difficult to say if concurrent HNF4A mutation which can present with hyper-insulinemic hypoglycemia in neonatal period has any implication for low sulfonylurea dose requirement.

Conclusion Genetic diagnosis has significant therapeutic implications in management of neonatal diabetes. Majority of infants with neonatal diabetes due to specific mutations known to respond oral formulation and can be managed without insulin. Timely diagnosis and treatment will result in better glycemic control and reduced morbidity.