title: A novel insulin receptor mutation in an adolescent with acanthosis nigricans and hyperandrogenism.
abstract: Insulin receptor mutations cause extreme insulin resistance resulting in acanthosis nigricans and hyperandrogenism. We report a pre-menarchal adolescent female with normal weight, with severe acanthosis nigricans, acne, and hirsutism. Initial investigation revealed elevated fasting and post-prandial insulin and high testosterone and androstenedione levels. Her father had frequent complaints of hypoglycemia. Coding sequence and splice junction analysis of the INSR gene, in our patient and her father, revealed a heterozygous missense mutation in the β subunit of the insulin receptor (Arg1131Trp), resulting in receptor loss of function. Metformin therapy and carbohydrate control improved acanthosis and menarche ensued within 3 months. Our case highlights the importance of distinguishing insulin resistance commonly associated with obesity from monogenic defects. Although, there is no consensus on treatment of children with monogenic forms of insulin resistance due to its rarity, dietary and lifestyle modifications and insulin-sensitizing agents play a key role in management.
authors: Mansa
authors: M
authors: Krishnamurthy
authors: Mia M
authors: MM
authors: Pingul
mesh_terms: D000052:Acanthosis Nigricans / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000728:Androgens / Q000097:blood; D015703:Antigens, CD / Q000235:genetics*; D002648:Child; D005260:Female; D006628:Hirsutism / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000235:genetics*; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D015703:Antigens, CD; D013739:Testosterone; C435941:INSR protein, human; D011972:Receptor, Insulin