HNF1A mutation presenting with fetal macrosomia and hypoglycemia in childhood prior to onset of overt diabetes

Abstract

HNF1A-MODY (MODY3) is a common subtype of autosomal dominant diabetes. Unlike HNF4-MODY where fetal macrosomia and early postnatal hyperinsulinemic hypoglycemia have been reported, a history of transient insulin overproduction has not been recognized in individuals with HNF1A-MODY yet. Here, we report a 40-year-old male patient with HNFJA mutation p.Arg272His (c.815G>A) with a history of fetal macrosomia (4750 g, 59 cm) and, at least, one attack of symptomatic hypoglycemia in childhood. Diabetes was subsequently diagnosed at 19 years. The proband's daughter who developed diabetes at 16 years carries the same mutation, but her birth weight and length were in the upper normal range, and she never experienced hypoglycemic symptoms. The observation of fetal macrosomia and hypoglycemia in childhood is suggestive of a biphasic impact of the HNF1A mutation on beta-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.