Abstract Objective Donohue syndrome and Rabson-Mendenhall syndrome are extreme forms of insulin resistance caused by biallelic mutations in the insulin receptor gene. Recombinant human IGF1 (rhIGF-1) treatment is often used but its long-term benefits and risks are still poorly delineated. We describe rhIGF-I treatment outcomes of a cohort of patients with Donohue syndrome and Rabson-Mendenhall syndrome, and compare them to previously published patients. Design Single-centre retrospective observational study. Methods Case note review. Literature search for previously published Donohue syndrome and Rabson-Mendenhall syndrome patients treated with rhIGF-1. Results rhIGF1 outcomes beyond 4 months have been reported for only 11 patients with Donohue syndrome and Rabson-Mendenhall syndrome to date. We provide outcome data for three more males, and report the long-term clinical course of a patient already described. Metabolic benefits of rhIGF-1 included improved glycaemic control and fasting tolerance in early years of life, and some growth enhancement. Two patients exhibited poor response or intolerance to rhIGF-1 and died in infancy. The two longest-lived patients had progressive decompensation to diabetes mellitus, in one case despite long-term uninterrupted rhIGF-1 therapy. We also describe new features associated with severe insulin receptoropathies, such as cataract, liver haemangioma, and impaired hepatic protein synthesis. Conclusion The phenotypes of Donohue and Rabson-Mendenhall syndromes are heterogeneous. Current treatment options remain unsatisfactory as high dose rhIGF-1 exerts only limited beneficial effects and does not prevent decompensation to diabetes mellitus. More research is needed to identify alternative treatment strategies for extreme forms of insulin resistance.
Improda et al. (Tue,) studied this question.