ESPE Abstracts (2019) 92 FC9.2

ESPE2019 Free Communications Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) (6 abstracts)

Heterozygous Insulin Receptor (INSR) Mutation associated with Neonatal Hyperinsulinaemic Hypoglycaemia and Familial Diabetes Mellitus

Aashish Sethi 1 , Syed Haris Ahmed 2 , Kevin Colclough 3 , Mohammed Didi 1 , Sarah Flanagan 3 & Senthil Senniappan 1


1Alder Hey Children Hospital, Liverpool, United Kingdom. 2Countess of Chester Hospital, Chester, United Kingdom. 3University of Exeter Medical School, Exeter, United Kingdom

Introduction: Mutations in Insulin Receptor (INSR) is usually associated with insulin resistance and hyperglycemia. Homozygous or compound heterozygous mutations in INSR are usually linked with Rabson-Mendenhall or Donohue syndromes whilst heterozygous INSR mutations are associated with type A insulin resistance. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycemia (HH) have been described in adults and children but not in the neonatal period. The youngest age reported with HH and heterozygous INSR mutation is 3 years.

Case Presentation: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent neonatal hypoglycemia and was diagnosed with HH. The child's maternal grandfather had been diagnosed with type 2 diabetes mellitus at the age of 45 years and was treated with metformin. A good response to diazoxide was noted in the infant and on subsequent follow up, diazoxide was gradually weaned and discontinued by 8 months of age. The couple's second child presented with SGA and HH at birth responsive to diazoxide which remitted at 10 months of age. Both infants tolerated a 16 hour fast without hypoglycemia and with normal concentrations of plasma insulin and demonstrated no clinical evidence of insulin resistance at 2 and 4 years of age. The mother had normal body mass index (BMI 24 kg/m2). Maternal grandfather of the infants had a BMI of 25 kg/m2. Neither adult showed clinical signs of insulin resistance. On genetic analysis, a heterozygous pathogenic INSR missense variant p.(Met1180Lys) was found in both infants, mother and grandfather, but not in the father.

Conclusion: We report, for the first time, an association between INSR mutation and transient neonatal HH. INSR mutations should be considered in patients with neonatal HH and a family history of diabetes mellitus. Follow up of these children is important to determine the natural history of progression and early diagnosis of diabetes or insulin resistance.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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