ESPE Abstracts

Background: Donohue syndrome (DS) is caused by autosomal-recessive loss of function mutations of the insulin receptor gene. DS is associated with diabetes mellitus unresponsive to conventional insulin therapy due to severe insulin resistance. Patients exhibit IUGR and postnatal failure to thrive. They develop a characteristic facies, hypertrichosis and acanthosis nigricans. Most patients die within the first two years of life because of respiratory infections. To date, no causal therapy is available.

Case report: The patient was born at term in Libya with a birth weight of 1300 g. Postpartally, he rapidly developed postprandial hyperglycemia. Despite high-caloric nutrition he exhibited severe and progressive dystrophy. Mutation analysis revealed a homozygote mutation in exon 2 of the INSR gene (c(591delC); p.(A198PFS*84)). First presentation in our institution was at 12 month of age with a weight of 3300 g. HbA1c was 10%, IGF-I and IGFBP-3 were below detection limits. We started a probatory therapy with rIGF-I (Mecasermin) s.c. twice daily (max. 515 mg/kg per day, bid). Since we were unable to achieve satisfactory glucose control we decided to switch towards continuous s.c. rIGF-I therapy via insulin pump. Mecasermin dosage was adapted throughout the day. A critical adverse effect of this regimen was the development of adenoid hyperplasia, requiring adenotonsillectomy. Within 9 months, we saw an improvement of HbA1c from 9.7 to 7.6% and a weight gain from 3.3 to 5.2 kg body weight. Unfortunately, the patient died at an age of 23 months in Libya during the course of a respiratory infection.

Conclusion: Using s.c. rIGF-I therapy we observed a significant improvement of glucose homeostasis and moderate weight gain. Therefore we consider that a trial with continuous Mecasermin via insulin pump should be considered in patients with DS.