ESPE Abstracts (2015) 84 P-2-250

Recombinant Human IGF1 Treatment in Patients with Insulin Receptor Mutations Resulting in Donohue Syndrome: A 10-Year Experience in a Tertiary Centre

Nicola Improdaa, Harshini Katugampolaa, Pratik Shaha,b, Hannah Gordona, Rakesh Amina,b, Catherine J Petersa,b, Robert K Semplec & Mehul T Dattania,b

aLondon Centre for Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Trust, London, UK; bInstitute of Child Health, London, UK; cDepartment of Clinical Biochemistry, University of Cambridge, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK

Background: Donohue syndrome (DS) is the most severe form of insulin-resistance due to autosomal recessive mutations in the insulin receptor gene. Previous reports demonstrate a role for recombinant human IGF1 (rhIGF1), however optimal treatment strategy remains unclear.

Case series: Four males with DS have been treated with bolus rhIGF1 (see table below). They had no IGF1 response on an IGF1 generation test. No long-term side effects of rhIGF1 were reported.

Conclusion: High dose rhIGF1 is safe and can mitigate metabolic abnormalities in patients with DS. We report survival into adolescence in a patient with no severe comorbidities, in whom the fast tolerance dramatically improved on rhIGF1 and long-term growth was relatively preserved. Although a twice daily regimen is the most frequently reported, 8 h administration may be required to optimise metabolic control, as demonstrated in Patient 2.