Abstract

*G. Sruthi, O. Saraswathi, C. Mohana

ABSTRACT

Insulin resistance caused by rare genetic conditions are the group of inherited metabolic disorders that are characterized by the fact that the body does not respond to insulin properly although there are normal or very high levels of insulin in the blood. These disorders are mainly caused by mutations in the insulin receptor or in the signalling molecules that are involved after the receptor and they are accompanied by severe metabolic complications. Leprechaunism or Donohue syndrome is the most extreme phenotype in this group of disorders and it is significantly due to homozygous or compound heterozygous mutations in the INSR gene. Affected Patients mostly represents with intrauterine growth retardation (IUGR), dysmorphic features, severe hyperinsulinemia, multi-organ involvement in the neonatal period and there is a high mortality rate during the first few years of life. This review mainly focuses on classification, molecular genetics, and clinical manifestations of rare genetic insulin resistance disorders, particularly Leprechaunism. Diagnostic approaches, management strategies in vogue, and emerging therapies are also discussed. The understanding of these rare disorders will not only assist in early diagnosis, proper genetic counselling, and targeted therapy but will also grant new insights into the disease mechanisms. Furthermore, Research is required to enhance the clinical outcomes and quality of life in the affected patients.