Work

Report of Prolonged Neonatal Hypoglycemia in Three Infants of Mothers With Variants in HNF1A

Year: 2022

Type: article

Abstract: Background/Objective Genetic variants in hepatic nuclear factor 1α ( HNF1A ) cause maturity-onset diabetes of the young (MODY). We sought to examine whether HNF1A MODY variants also cause neonatal hypoglycemia. Case Report We present 3 infants with variants in HNF1A shared with their mothers. The infants experienced neonatal hypoglycemia, 2 extending beyond 1 year and the third resolving by 28 days, and all were large for gestational age (birth weights of >99th percentile) . In 2 cases, genetic testing for neonatal hypoglycemia revealed pathogenic variants in HNF1A ; 1 mother was previously diagnosed with HNF1A MODY, and the other's genetic testing and ultimate MODY diagnosis were prompted by her child's hypoglycemia workup. In the third case, the infant's persistent hypoglycemia prompted genetic testing, revealing an HNF1A variant of uncertain significance, which was then identified in the mother. Discussion Genetic variants causing HNF1A MODY have not been definitively linked to neonatal hypoglycemia or fetal overgrowth in utero. MODY caused by HNF1A is clinically similar to that caused by HNF4A , for which a causal relationship with neonatal hypoglycemia is more certain. Case reports have previously implicated variants in HNF1A in congenital hyperinsulinism; however, these cases have generally not been in families with MODY. The cases presented here suggest that HNF1A variants causing MODY may also cause neonatal hypoglycemia. Conclusion Although confounding factors make the assessment of neonatal hypoglycemia challenging, these cases offer potential support for single genetic variants in HNF1A causing both MODY and neonatal hypoglycemia, with associated fetal overgrowth in utero.

Source: AACE Clinical Case Reports

DOI: 10.1016/j.aace.2022.07.004