Severe progressive obstructive cardiomyopathy and renal tubular dysfunction in Donohue syndrome with decreased insulin receptor autophosphorylation due to a novel INSR mutation.

Abstract

UNLABELLED:

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.

• Authors: Tinka Hovnik, Nevenka Bratanič, Katarina Trebušak Podkrajšek, Jernej Kovač, Darja Paro, Tomaž Podnar, Nataša Bratina, Tadej Battelino
• Journal: European journal of pediatrics (Eur J Pediatr) Vol. 172 Issue 8 Pg. 1125-9 (Aug 2013) ISSN: 1432-1076 [Electronic] Germany
• PMID: 23229189 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins
• myotrophin
• Insulin-Like Growth Factor I
• Propranolol
• Receptor, Insulin

Topics

• Cardiomyopathy, Hypertrophic (drug therapy, genetics, metabolism)
• Donohue Syndrome (genetics, metabolism)
• Fatal Outcome
• Growth Disorders (genetics, metabolism)
• Humans
• Insulin Resistance (genetics)
• Insulin-Like Growth Factor I (therapeutic use)
• Intercellular Signaling Peptides and Proteins (therapeutic use)
• Mutation, Missense
• Propranolol (therapeutic use)
• Receptor, Insulin (genetics, metabolism)