ESPE Abstracts

Background: Leprechaunism, due to a mutation of both alleles of insulin receptor gene, is a most severe and precociously life-threatening condition, difficult to treat.

Objective and hypotheses: In leprechaunism rhIGF1 may replace insulin through I the insulin-like metabolic properties of its own receptor.

Method: rh IGF1 was continuously subcutaneously administered through a.pump from the age of four months and adjusted according to 2–3 S.D. plasma IGF1 levels from a 300 to 400 μg/kg per day.

Results: Case report: a first pregnancy of unrelated French Caucasian healthy parents was marked by a severe intrauterine growth retardation. All birth measurements at normal term were – 4 SDS. Immediately were noticed typical dysmorphic signs of leprechaunism. The alternance of fasting intolerance, and of ketotic hyperglycaemia, became soon evident. Insulin and C-peptide levels were extraordinarily high, respectively 14 000 U/l and 30 ng/ml. IGF1 was undetectable in the plasma and leptin was present, 2.5 mg/l. She is heterozygous composite for mutations of the insulin receptor gene coding for V555D in the insulin-binding domain, coming from her father and A1055V in the tyrosine kinase domain, coming from her mother. Under continuous enteral nutrition, metformin corrected hyperglycaemia but not hyperinsulinaemia. Extension investigations evidenced the persistence of growth retardation, hypotonia, hypertrophic cardiomyopathy, bulky multifollicular ovaries at US, hyperandrogenism, hypercalciuria with low parathyroid hormone levels and nephrocalcinosis, treated by bisphosphonates. rhIGF1 administration medication allowed insulin levels to fall to 1000 U/l levels, without worsening of hyperglycaemia. Cardiomyopathy was contained with the help of a beta adrenergic blocking agent, lipoatrophy disappeared, leptin levels doubled, growth improved, ovary volume halved, hyperandrogenism vanished, but adenoids grew dramatically, needing several nasal curettages.

Conclusion: In leprechaunism, early rh IGF1 administration improves growth, adipogenesis, hyperinsulinaemia and ovarian hyperstimulation but adverse effects may occur, linked either to this medication or to the natural evolution of the condition.