EFFECT OF INTRAVENOUS INSULIN-LIKE GROWTH-FACTOR-I IN 2 PATIENTS WITH LEPRECHAUNISM

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 mu g/kg/h, respectively. Although supraphysiologic concentrations of IGF-I were achieved (459 and 1583 mu g/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.