Aim: We aimed to report the clinical and laboratory characteristics of a patient with severe congenital insulin resistance syndrome due to a compound heterozygous c.836G>A & c.1268+2T>A mutation in INSR gene.
Case: A female patient presented with hyperglycemia at postnatal 36th day. She was born to non-consanguineous Turkish parents after a 39 week uneventful gestation via normal spontaneous vaginal delivery. Her birth weight was 2700 g. At presentation, she had coarse facies, abdominal distention, umbilical hernia, and macroglossia. Laboratory examination revealed blood glucose of 393 mg/dL, insulin >300 µIU/mL, and C-peptide >20 ng/mL (0.9-4). She was started on regular insulin and subsequently subcutaneous NPH-insulin. Insulin requirement was decreased gradually from 2.5 unit/kg/day to 0.5 unit/kg/day at the first month and stopped at 2.5 months. During follow up, she developed acanthosis nigricans and fasting hypoglycemia suggesting insulin resistance syndrome. Molecular genetic analysis: Sanger sequence analysis of the KCNJ11, ABCC8 and INS genes did not identify a mutation. Analysis of all the coding regions and exon/intron boundaries of the monogenic diabetes genes by targeted next-generation sequencing revealed a compound heterozygous missense c.836G>A (p.R279H) variant in exon 3 and a splicing c.1268T>A variant in exon 5 of INSR gene.
Conclusion: Mutations in the INSR cause severe congenital insulin resistance syndromes which may lead to intrauterine and postnatal growth retardation, acanthosis nigricans, fasting hypoglycemia, and postprandial hyperglycemia. At neonatal period, patients may present with clinical findings of neonatal diabetes and develop the specific clinical findings of insulin resistance (e.g. acanthosis nigricans) during follow-up.