Effect of intravenous insulin-like growth factor I in two patients with leprechaunism

Abstract

Leprechaunism (Donohue syndrome) is an autosomal recessive disorder characterized by hyperglycemia, extreme insulin resistance, dysmorphic features, failure to thrive, and early death. In this study, recombinant IGF-I, which has both insulin-like and anabolic effects, was administered to two infants with leprechaunism in an attempt to reduce hyperglycemia and improve nutritional status. IGF-I was infused for 66 h in patient FL-1 and 62 h in patient NC-2, with maximal infusion rates of 110 and 40 micrograms/kg/h, respectively. Although supraphysiologic concentrations of IGF-I were achieved (459 and 1583 micrograms/L in FL-1 and NC-2, respectively), there were no apparent glucose-lowering or nitrogen-sparing effects. Insulin concentrations decreased from extremely high values (16804 and 10224 pmol/L) but remained elevated (611 pmol/L in FL-1 and 5869 pmol/L in NC-2). No changes in serum and urinary urea nitrogen or electrolytes occurred. IGF binding protein-2, which was the predominant IGF binding protein in serum by ligand blot and immunoblot, did not change with IGF-I infusion. IGF binding protein-3 levels were low at baseline and increased slightly during the infusion. We hypothesize that the lack of significant glucose-lowering and anabolic responses to IGF-I could be secondary to a postreceptor defect in IGF-I signaling resulting from the absence of functional insulin receptors.