Keywords
Donohue Syndrome
Insulin Receptor
Acanthosis Nigricans
Diagnosis
Pathophysiology
Genetics
Pharmacological Treatment
How to Cite
Abstract
Background: Genetic insulin resistance syndrome is a rare and underdiagnosed entity with variable clinical manifestations that go beyond glucose homeostasis disorders.
Purpose: To conduct a narrative review of the pathophysiology, genetics, clinical manifestations, diagnosis, and treatment of severe insulin resistance syndromes linked to mutations of the insulin receptor gene (INSR).
Methodology: Review of the literature in the PubMed database, Scielo , and gray literature in the serach engine of the repository of Universidad Nacional de Colombia. We use the MeSH terms: "Insulin Resistance", "Donohue syndrome", "Receptor, Insulin", “Physiopathology”, “signs and symptoms”, “Diagnosis”, "Genetics", “Pharmacological Treatment”, and review of the reference list ("snowball") of the selected studies.
Results: Severe insulin resistance syndromes linked to insulin receptor mutations comprise a spectrum of genetic conditions caused by pathogenic variants in the INSR that can manifest in a continuum of clinical features and biochemical abnormalities from life-threatening forms in the neonatal period to mild forms that can be underdiagnosed and confused with type 2 diabetes. Treatment of these conditions is based on a pathophysiological approach and anecdotal reports rather than evidence from clinical trials.
Conclusion: Given the rarity of insulin resistance syndromes linked to abnormalities of the insulin receptor gene, their diagnosis and treatment remain a challenge in clinical practice.
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