Open AccessUnusual Glycemic Presentations in a Child with a Novel Heterozygous Intragenic INSR Deletion
Author(s) -
Federica Verdecchia,
Neşe Akcan,
Antonia Dastamani,
Kate Morgan,
Robert K. Semple,
Pratik Shah
Publication year - 2020
Publication title -
hormone research in paediatrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.816
H-Index - 89
eISSN - 1663-2826
pISSN - 1663-2818
DOI - 10.1159/000510462
Subject(s) - medicine , endocrinology , hyperinsulinemic hypoglycemia , hypoglycemia , postprandial , insulin , insulin resistance , type 2 diabetes , hyperinsulinism , metformin , acanthosis nigricans , glycemic , insulin receptor , insulin tolerance test , diabetes mellitus , insulin sensitivity
Background: Mutations of the insulin receptor (INSR) gene lead to a wide spectrum of inherited insulin resistance (IR) syndromes. Among these, type A-IR, usually caused by dominant negative INSR mutations, generally presents peri-pubertally in girls. Case: A 2.8-year-old girl was referred due to recurrent postprandial and fasting hypoglycemia. She had been born at full-term with birth weight 1.89 kg, and had developed transient neonatal diabetes. Examination showed satisfactory growth, reduced adipose tissue, acanthosis nigricans, and isolated thelarche. After 12 h of fasting, she developed hypoglycemia (glucose 2.8 mmol/L), with inappropriately raised plasma insulin concentration of 5.4 mU/L and suppressed fatty acids and ketone bodies. Oral glucose tolerance testing showed severely increased plasma insulin concentration (>300 mU/L) with hypoglycemia (glucose 1.6 mmol/L) at 2.5 h. She was initially managed on dietary modifications, cornstarch, and then trialed on acarbose for postprandial hyperinsulinemic hypoglycemia (PPHH) with some response. However, she was noted to have increased frequency of hyperglycemia after a couple of years of treatment. She was then switched to metformin and continued to have dietary carbohydrate modification including cornstarch that improved fasting tolerance, hyperglycemia, and postprandial hypoglycemia. Genetic testing identified heterozygous deletion of the last exon of the INSR gene, exon 22. Conclusion: We present a case of type A-IR, caused by a novel INSR deletion, presenting unusually early with transient neonatal diabetes, followed by episodes of hypoglycemia and hyperglycemia during later childhood. Early life presentations, including neonatal diabetes and PPHH, should lead to consideration of type A-IR.