A novel heterozygous mutation in the insulin receptor gene presenting with type A severe insulin resistance syndrome.
Arameh S AghababaieMartha Ford-AdamsCharles R BuchananVed B AryaKevin ColcloughRitika R KapoorPublished in: Journal of pediatric endocrinology & metabolism : JPEM (2020)
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.
Keyphrases
- type diabetes
- insulin resistance
- glycemic control
- case report
- early onset
- adipose tissue
- high fat diet
- genome wide
- metabolic syndrome
- cardiovascular disease
- copy number
- polycystic ovary syndrome
- skeletal muscle
- high fat diet induced
- body mass index
- weight loss
- bone marrow
- photodynamic therapy
- autism spectrum disorder
- cancer therapy
- genome wide analysis
- drug induced
- circulating tumor