title: 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.
authors.affiliation: Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7220.
authors.forename: P F
authors.initials: PF
authors.lastname: Backeljauw
authors.forename: C
authors.initials: C
authors.lastname: Alves
authors.forename: M
authors.initials: M
authors.lastname: Eidson
authors.forename: W
authors.initials: W
authors.lastname: Cleveland
authors.forename: L E
authors.initials: LE
authors.lastname: Underwood
authors.forename: M L
authors.initials: ML
authors.lastname: Davenport
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007333:Insulin Resistance; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D013577:Syndrome
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I