ESPE Abstracts (2019) 92 P3-266

ESPE2019 Poster Category 3 Late Breaking Abstracts (69 abstracts)

A Novel Mutation of INSR Gene in a Child with Type A Insulin Resistance

Federica Verdecchia 1 , Nese Akcan 1 , Antonia Dastamani 1 , Kate Morgan 1 , Robert Semple 2 & Pratik Shah 1,3

11. Endocrinology Department, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom. 23. Chair of Translational Molecular Medicine, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. 32. Genetics and Epigenetics in Health and Disease Section, Genetics and Genomics Medicine Program, UCL GOS Institute of Child Health, London, United Kingdom

Background:Mutations of insulin receptor gene (INSR) lead to a wide spectrum of inherited insulin resistance syndromes. Type A insulin resistance is one of the these syndromes which is inherited autosomal dominant and leads to mild clinical symptoms after puberty.

Objective and Hypothesis: To report a novel mutation of INSR gene mutation in a case of Type A insulin resistance who presented with transient neonatal diabetes and then episodes of hypoglycemia and hyperglycemia during childhood.

Case: A full-term Afro-Caribbean female infant, of birth weight 1.89kg, developed transient neonatal diabetes with negative genetic testing (microarray, TNDM 6q methylation analysis).At the age of 2.8 years, she presented with episodes of postprandial and fasting hypoglycemia. Her examination showed satisfactory growth, lipodystrophy, acanthosis nigricans and isolated thelarche. Further investigations demonstrated that the child after 12 hours of fasting developed hypoglycemia (glucose 2.8mmol/L), with inappropriately raised insulin level of 5.4mU/L. Her oral glucose tolerance test (OGTT) showed excessively high levels of insulin throughout the test (>300mU/L) along with hypoglycaemia (glucose 1.6mmol/L) at 2.5 hours of the test. The mixed meal test also confirmed the diagnosis of postprandial hyperinsulinemic hypoglycemia (PPHH). She had negative genetic analysis for Familial Lipodystrophy (LMNA and PPARG genes) and Hyperinsulinism (ABCC8 and KCNJ11 genes). At the age of 5.1 years she started acarbose treatment for the management of PPHH that lasted for two years. Subsequently, she developed frequent episodes of hyperglycemia along with postprandial and fasting episodes of hypoglycemia recorded persistently on continuous glucose monitoring. Her HbA1c and fasting lipids remained within the normal range. She had continuously suppressed androgens and her pelvic ultrasound showed pre-pubertal appearance of her internal genitalia until the age of 8.7 years. She has normal baseline pituitary function and her LHRH showed predominant FSH response. Treatment of metformin along with carbohydrate diet modification and corn starch started at the age of 7 years not only improved fasting tolerance but also episodes of hyperglycemia and post-prandial hypoglycemia. Genetic testing identified a novel heterozygous deletion of exon 22 in INSR gene.

Conclusion: The present case details the clinical features of a patient with genetically proven Type A insulin resistance. Early age manifestation, neonatal diabetes and also PPHH can be another presentation of this disease. Children with this can be quite challenging to manage using pharmacotherapy and dietary modification. Further accumulation of genetically proven cases and long-term treatment outcomes following early diagnosis are required to understand the dynamics of this disease.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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