Homozygous mutation of Insulin receptor (INS-R) gene cause an extremely rare disease called Leprechaunism, and induce intrauterine growth restriction with poor postnatal growth, hyperinsulinemia, postprandial hyperglycaemia, pre-prandial hypoglycaemia, typical facies, lack of subcutaneous fat, thick skin, hypertrichosis, macrogenitosomia in males. The survival is severely compromised in these patients. Treatment with diazoxide could ameliorate glycaemic control, however these patients are signed by a high precocious lethality into the first 12 years of life. Anecdotical cases are described with a longer survival. We describe the clinical case of a child with Leprechaunism, born from consanguineous parents, who had a homozygous mutation of the INS-R gene: c.3289 C>T (CAG->TAG) p.Gln 10975 stop (Q1097X). He was treated with diazoxide (5 mg/kg per day) and captopril (0.04 mg/kg per day), with a reduction of hyperglycaemia and hypertension. However, the stop in ponderal and linear growth induced to try the off-label treatment with mecasermin (0.04 mg/kg bid). The dose was progressively increased to 0.06 mg/kg/bid. After 2 years of treatment with mecasermin, the child increased the weight to 5.9 kg, length to 65 cm, head circumference to 41 cm. His neuromotor development is significantly improved. He performed an encephalic MRI which showed non-specific alterations of the white matter subcortical and periventricular, possible evolution of neonatal prolonged hypoglycaemic events. The peculiar outcome of our patient is linked to the long-term survival and the clinical improvement by mecasermin.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology