P287 Transient neonatal hyperinsulinaemic hypoglycaemia secondary to a hnf1a gene mutation. (June 2019)

• Record Type: Journal Article
• Authors: Sheridan, Sabrina; McCarron, Laura; O'Donnell, Gillian; Carolan, Eirin; Murphy, Nuala P
• Is Part Of: Archives of disease in childhood. Volume 104:(2019)Supplement 3
• Page Start: A272
• Page End: A272
• Publication Date: 2019-06
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2019-epa.637
• Languages: English
• ISSNs: 0003-9888

Abstract

Abstract : Introduction: Monoallelic pathogenic variants in HNF1A are a well-established cause of maturity-onset diabetes of the young 3 (MODY3). These variants are rarely reported as a cause of neonatal hyperinsulinaemic hypoglycaemia (NHH). Case Description: A term infant was delivered by spontaneous vaginal delivery with a birth weight of 3.53 kg (50 th centile). He was born to a Gravida 2 Para 1 mother who had manifested gestational diabetes that necessitated insulin therapy in the first trimester of both of her pregnancies. His older sibling also had transient neonatal hyperinsulinism that fully resolved at 1 month of age. He was admitted to the NICU for the management of transient tachypnoea of the newborn. The infant developed symptoms of hypoglycaemia at 1 hour of life and blood glucose level was measured at 0.4 mmol/L. He continued to become hypoglycaemic despite high glucose infusion rates (GIR). Critical samples were collected whilst hypoglycaemic (plasma glucose 1.7 mmol/L) on day 3 of life confirming the diagnosis of non-ketotic hyperinsulinaemic hypoglycaemia. Given the family history samples from the infant and his parents were sent to Exeter Clinical Laboratory for hyperinsulinism genetic testing. He was commenced on diazoxide therapy at 3 mg/kg/day on day 17 of life and following this therapy his blood glucose levels normalised on 4 hourly oral feeds (GIR = 8.3 mg/kg/min). He successfully tolerated an 8 hour safety fast and was discharged home on day 31 of life. At 7 weeks of life he presented unwell, febrile and hyperglycaemic (blood glucose range 18–22 mmol/l). He had a urinary tract infection and was commenced on antibiotic therapy. His diazoxide dose was discontinued. Close blood glucose observation over a 7 day period and a repeat safety fast demonstrated normoglycaemia. Genetic testing subsequently demonstrated that both the infant and his mother were heterozygous for a pathogenic HNF1A missense variant (NM_000545.6:c.788G>Ap.(Arg263His). Discussion: NHH causes significant morbidities including adverse neurodevelopmental sequelae and mortality if untreated. Transient NHH is commonly observed in infants of mothers who have gestational diabetes. HNF1A gene mutation however is a rare cause of transient NHH. Identification of this genetic diagnosis has had major implications for this infant and his family. His mother is currently being appropriately treated for MODY3 and has been counselled about the 50% recurrence risk in subsequent pregnancies. Both children will be observed closely from late childhood due to their risk of developing MODY3.