SUN-272 Persistent Hyperinsulinemic Hypoglycemia Due to Mutation in Hepatocyte Nuclear Factor 4A

• Published in: Journal of the Endocrine Society 2019-04, Vol.3 (Supplement_1)
• Main Authors: Vlachopapadopoulou, Elpis, Dikaiakou, Eirini, Athanasouli, Fani, Sifianou, Popi, Sertedaki, Amalia, Michalacos, Stefanos
• Format: Article
• Language: English
• Subjects: Pediatric Endocrinology
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/js.2019-SUN-272

Background: Congenital hyperinsulinism (HI) is the most common cause of hypoglycemia in children. Delay in diagnosis and or inadequate management can lead to brain damage. Persistent hyperinsulinemic hypoglycemia of infancy is a genetic disorder with both familial and sporadic form. Aim: To present the case of an infant with persistent hyperinsulinenic hypoglycemia due to HNF4A gene mutation, inherited by his mother who was perceived to have Diabetes Mellitus Type 2. Clinical presentation: A premature boy born at 35 weeks gestation by caesarian section due to mother’s hypertension, proteinuria and peripheral edema with birth weight of 2565gr and 44.5cm length. He was the first child of family and mother is referred to suffer from diabetes mellitus type 2 since 17 years of age treated with oral antidiabetic drugs. During pregnancy, optimal glycemic control was achieved after initiation of insulin therapy. After birth, at first 2 hours of life, blood glucose was 23mg/dl. Asymptomatic hypoglycemia persisted. During hypoglycemia arterial pH, lactic acid and cortisol were within reference range and insulin as ell c-peptide levels were elevated. Synachten test was normal. 30 minutes after glucagon administration, glucose level was increased by 48mg/dl and after 60 minutes glucose level was increased by 34 mg/dl. Five hours after feeding, glucose was 47mg/dl and diazoxide treatment was started (7.5 mg/kg/day). He responded well to diazoxide and daily dosage was decreased to 1mg/kg/day. Genetic testing was performed. Heterozygous mutation in c.998G>C, pR333P of HNF4A gene was identified to infant and his mother. The infant is now 8 months old and he continuous on diazoxide therapy growing well. The identification of the mutation clarified that the mother suffers from maturity- onset diabetes of the young (MODY) and not Diabetes Mellitus type 2. Conclusion: Early detection of HI is very important in order to prevent permanent sequelae. Genetic mutation testing should be performed in order to define best treatment approach. Family history of diabetes can elucidate that the affected gene is HNF4A or HNF1a. HI due to HNF4A mutations may be transient or persistent into childhood and is usually responsive to diazoxide therapy. MODY can develop during the second or third decade of life that is usually responsive to sulfonylurias. Reference: Stanley CA Perspective on the genetics and diagnosis of congenital hyperinsulinism disorders JCEM 2016; 101: 815-26