Donohue 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.
CONCLUSION: Treatment 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.