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

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.

<p>Recent Advances in Neonatal Diabetes</p>

“…5,14 Common clinical manifestations include being small for gestational age due to prenatal intrauterine growth restriction from deficiency of functional insulin which is important for in-utero growth. 15 Another common clinical manifestation is poor postnatal growth or failure to thrive and behavioral changes such as irritability and polyuria. Infants with DKA may have few nonspecific symptoms such as tachypnea, lethargy, irritability, and sunken fontanels and eyes.…”

“…37 The starting dose recommended for these rapid-acting insulin is 0.1 to 0. 15 blood glucose values be checked at least initially, though insulin may be needed with every other feed only (3-4 times per day). Administration of short-acting insulin before each feed may result in stacking of insulin and resultant hypoglycemia.…”