Different clinical characteristics of type A insulin resistance syndrome

Insulin resistance (IR) type A is an autosomal dominant condition with a prevalence of 1/100 thousand people. It’s associated with a defect in the insulin receptor gene INSR. It’s more often diagnosed among young women due to hyperandrogenism. In men, the disease is usually diagnosed only after they develop diabetes mellitus.

The article presents clinical cases reports of IR type A in an adolescent girls with no obesity and prediabetes and diabetes. Patient 1, 17.9 years old presented complaining of acne, darkening of the skin on armpits, back of the neck, groins, elbows, inner thighs. Her fasting insulin was 101 µed/ml (HOMA-IR 18,9). 2 hours after glucose loading insulin was at the level of 684 µed/ml. Patient 2 — 16.6 years old, presented with the complaints of an irregular menstrual cycle of up to 90 days. She had no excess weight (SDS BMI = -0.7 SD). Multiple skin papillomas were observed. Laboratory and ultrasound signs of polycystic ovary syndrome were revealed, as well as normoglycemia and severe IR (up to 366 μU/ml during oral fasting glucose tolerance test). In both patients, the diagnosis was confirmed by the results of genetic testing. Patient 1 was diagnosed with a pathogenic heterozygous defect in exon 19 of the INSR insulin receptor gene (NM 000208.4, ch19:7122707C>T, c.3436G>A), leading to an amino acid substitution at protein position 1146 (p.Gly1146Arg). Patient 2 revealed a heterozygous variant unknown clinical significance in exon 17 of the INSR gene (NM 000208.4) c.3095G>A (HG38, chr19:7125446C>T), leading to the amino acid substitution of glycine for aspartate at position 1032 (p.Gly1032Asp). Metformin off-label therapy (1,500–2,000 mg per day) was initiated in both girls.

Presented clinical case reports demonstrate different patient complaints and clinical characteristics of type A insulin resistance syndrome. Patients with type A IR need personalized approach. High-dose metformin therapy can be used to reduce the severity of IR-associated skin symptoms such as acanthosis nigricans, papillomatosis, and polycystic ovary syndrome. Genetic diagnosis allows determining the prognosis and providing genetic counseling.

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