A novel heterozygous mutation in the insulin receptor gene presenting with type A severe insulin resistance syndrome

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Authors
Colclough, Kevin
Journal
Journal of Paediatric Endocrinology and Metabolism
Type
Case Report
Publisher
Sheridan PubFactory
Rights
© 2020 Walter de Gruyter GmbH, Berlin/Boston.
Background Inherited severe insulin resistance syndromes (SIRS) are rare and can be caused by mutations in the insulin receptor gene (INSR). Case presentation A 12-year-old Jamaican girl with a BMI of 24.4 kg/m2 presented with polyuria and polydipsia. A diagnosis of T1DM was made in view of hyperglycaemia (18 mmol/l), and elevated Hba1C (9.9%), and insulin therapy was initiated. Over the next 2 years, she developed hirsutism and acanthosis nigricans, and had minimal insulin requirements with frequent post-prandial hypoglycaemia. In view of this, and her strong family history suggestive of a dominantly inherited type of diabetes, the diagnosis was revisited. Targeted next-generation sequencing (NGS) of the patient's monogenic diabetes genes was performed. What is new? NGS revealed a novel heterozygous missense INSR variant, NM_000208.3:c.3471T>G, p.(His1157Gln), confirming a diagnosis of Type A SIRS. Conclusions Type A SIRS can be difficult to differentially diagnose due to the variable phenotype. Features of insulin resistance may be absent at initial presentation and may develop later during pubertal progress. Awareness of the clinical features and comprehensive genetic testing are essential to identify the condition.
Citation
Aghababaie AS et al. A novel heterozygous mutation in the insulin receptor gene presenting with type A severe insulin resistance syndrome. J Pediatr Endocrinol Metab. 2020 May 22;33(6):809-812.
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