ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume: 14 Issue: 2 Year: 2022
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Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Syndrome of Congenital Insulin Resistance Caused by a Novel INSR Gene Mutation [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-37928 | DOI: 10.4274/jcrpe.galenos.2021.2021.0256

Syndrome of Congenital Insulin Resistance Caused by a Novel INSR Gene Mutation

Aleksandra Rojek1, Beata Wikiera2, Anna Noczynska2, Marek Niedziela3
1Poznan University of Medical Sciences, Institute of Pediatrics, Department of Pediatric Endocrinology and Rheumatology, 27/33 Szpitalna Street, 60-572 Poznan, Poland
2Wroclaw Medical University, Department of Endocrinology and Diabetology for Children and Adolescents, 13c Josef Hoene-Wronski Street, 50-376 Wroclaw, Poland
3Poznan University of Medical Sciences, Institute of Pediatrics, Department of Pediatric Endocrinology and Rheumatology, Karol Jonscher’s Clinical Hospital 27/33 Szpitalna Street, 60-572 Poznan, Poland

Mutations in the insulin receptor gene result in rare inherited syndromes causing insulin resistance, such as leprechaunism (Donohue syndrome), Rabson-Mendenhall syndrome and insulin resistance type A. Leprechaunism is an autosomal recessive disorder associated with extreme insulin resistance that leads to hyperinsulinemia, impaired glucose homeostasis, fasting hypoglycemia and postprandial hyperglycemia. Impaired insulin action causes prenatal and postnatal growth retardation. Lipoatrophy, dysmorphic facies, hypertrichosis, macrogenitosomia and hypertrophy of internal organs are also present. A male infant with congenital insulin resistance was born at term after a normal pregnancy with a weight of 1905 g (<3c), a length of 48 cm (<3c), and an Apgar score of 10. Intrauterine growth retardation, transient hypoglycemia, pneumonia, urinary tract infection and heart defects (PFO – patent foramen ovale; PDA - patent ductus arteriosus) were diagnosed after birth. At 5 weeks of age, he was admitted to the regional hospital with severe fever, diarrhea and dehydration. Hyperglycemia was observed (672 mg/dl), and insulin was administered. He was referred to a hospital at 7 weeks of age for suspected neonatal diabetes and hypertrophic cardiomyopathy. The physical examination revealed a loud systolic heart murmur, tachycardia,
tachypnea, dysmorphic facies, hypertrichosis, acanthosis nigricans, hypotonia, swollen nipples and enlarged testicles. Glycemic fluctuations (50-250 mg/dl) were observed. The serum insulin concentration was high (maximum 1200 IU/ml) at normoglycemia. Ultrasound of the heart confirmed progressive hypertrophic cardiomyopathy. Leprechaunism was confirmed by genetic analysis of the insulin receptor (INSR) gene, in which a novel c.320C>G; p. Thr107Arg homozygous missense mutation in exon 2 was found.

Keywords: Insulin receptor, insulin resistance, leprechaunism



Corresponding Author: Marek Niedziela, Poland
Manuscript Language: English
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