ESPE Abstracts

Introduction: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) is a rare syndrome that presents during early childhood and is associated with high morbidity and mortality. 40-50% of patients have neural crest tumours, most commonly ganglioneuromas or ganglio-neuroblastomas denoted by the suffix ROHHAD(NET) in a subset of patients. Currently, there is no specific diagnostic biomarker available and diagnosis is based on the clinical constellation of signs and symptoms. With no curative treatment for ROHHAD, management is largely supportive. The exact aetiology remains unclear but an autoimmune origin has been postulated and various immunosuppressive agents have been used with variable benefit.

Case: The patient presented in cardio-respiratory arrest at 4 years of age following a 6-month period of rapid weight gain. She weighed 27kg (>99.6^th centile for weight) and was on the 9^th centile for height (BMI 26.4kg/m2; SDS +3.1). Despite parental attempts at restricting calories and regular physical activity weight reduction had been unsuccessful. A cardio-pulmonary sleep study showed central hypoventilation and she was commenced on nocturnal bi-level non-invasive ventilation (BiPAP). She was diagnosed with central diabetes insipidus, hyperprolactinaemia (1700 mIU/l, NR <699) and subsequently growth hormone deficiency on glucagon stimulation testing (growth hormone peak 4.4 ug/L, NR >6.7 ug/L) therefore she will soon commence growth hormone therapy. MRI pituitary, abdomen and pelvis were normal except for generalised adiposity. Cytokine serology, taken when she was otherwise well, demonstrated elevated levels of interleukin-6 (25pg/ml, NR 0-2). The patient received two courses of rituximab (750g/m²) four weeks apart in an attempt to suppress any underlying immune dysregulation. Dietary intake was restricted to 60% recommended daily allowance. Following these interventions, weight reduced from well above the 99.6^th to the 50^th centile in nine months (BMI 17.8 kg/m²; SDS +1.35; SDS reduction -1.75). Repeat plasma cytokine profiling six-months after rituximab therapy showed that the IL-6 level had normalised (<1.44 pg/ml, NR 0-2).

Discussion: This case demonstrates a patient with obesity and hypoventilation due to ROHHAD presenting with respiratory arrest, who had normalisation of interleukin-6 levels and successful weight reduction following treatment with rituximab and ongoing calorie restriction. This clinical response possibly reflects an underlying, immune-inflammatory pathology driving excess adiposity in this condition. Potentially, other aspects of the syndrome may also be mediated through immune dysregulation in which case rituximab may provide benefits for prognosis and survival.