• Tinka Hovnik, Nevenka Bratanič, Podkrajšek Katarina Trebušak KT, Jernej Kovač, Darja Paro, Tomaž Podnar, Nataša Bratina, and Tadej Battelino.
• Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, Bohoričeva 20, SI-1525, Ljubljana, Slovenia.
• Eur. J. Pediatr. 2013 Aug 1; 172 (8): 1125-9.

UnlabelledDonohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. We report a patient with pronounced clinical picture of leprechaunism who developed severe progressive hypertrophic obstructive cardiomyopathy (HOCM) and renal tubular dysfunction which improved on continuous subcutaneous infusion of recombinant human insulin-like growth factor-1 (rhIGF-I). INSR gene molecular analysis and insulin receptor (IR) autophosphorylation on cultured fibroblasts were performed. A novel homozygous missense mutation p.Leu795Pro was found, located in the extracellular portion of the β subunit of the insulin receptor. The post-binding defect of the insulin receptor signaling in cultured fibroblasts demonstrated decreased insulin receptor autophosphorylation.ConclusionTreatment with rhIGF-I partially reversed severe progressive HOCM and renal tubular dysfunction in a patient with Donohue syndrome associated with a novel p.Leu795Pro INSR gene mutation causing a severe decrease in IR autophosphorylation.

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