Endocrine Abstracts

JOINT353

Rabson-Mendenhall Syndrome (RMS) is a rare, autosomal recessive disorder caused by mutations in the INSR gene, leading to severe insulin resistance, dysmorphism and multisystemic complications. The features of RMS overlap with other metabolic and genetic disorders which can lead to delayed diagnosis. To our understanding, the twins presented in this case report are the youngest diagnoses of RMS globally. Lilac was brought to the attention of the general paediatricians with dysmorphic features, failure to thrive, developmental delay and significant polyuria and polydipsia. As her twin, Marigold, was found to have similar features, she was also investigated. A high HbA1c resulted in a referral to the diabetes team who put together the clinical features of dysmorphism, acanthosis nigricans and insulin resistance for a suspicion of Rabson-Mendenhall Syndrome; this was confirmed some months later for both fraternal twins by genetic testing. Following a difficult discussion explaining the diagnosis to parents, a multidisciplinary approach was taken that initially focused on continuous blood glucose monitoring to detect early morning hypoglycaemia and nutritional support. Metformin was started at 100 mg once-daily and then Increlex (Mecasermin) injections were started at 0.04 mg/kg once-daily under inpatient observation, titrated to 0.04 mg/kg twice-daily after six weeks. General monitoring for growth and development is ongoing. The early stage of RMS poses significant metabolic challenges due to early morning hypoglycaemia and postprandial hyperglycaemia and thus nutritional interventions are invaluable at this time. Early recognition and management of Rabson-Mendenhall Syndrome is extremely preferable over a presentation in treatment-resistant diabetic ketoacidosis which is often the case. Prompt diagnosis and use of targeted therapies can be essential in mitigating severe complications. Given the young age at diagnosis and the rarity of RMS, this case is being managed in collaboration with national experts however there is little evidence base for the treatments being offered. We hope this report will highlight the need for further research into novel therapeutic options and long-term management strategies for this challenging condition.