ESPE Abstracts

Introduction: Prader-Willi Syndrome (PWS) is characterized by severe neonatal hypotonia and feeding difficulty with subsequent hyperphagia, hypogonadism, and short stature. PWS has a prevalence of 1 in 10,000-30,000. Obesity-related complications occur from early childhood onwards. Liraglutide is a glucagon-like peptide-1 (GLP-1) analog that reduces appetite and body weight and improves glycemic control. Scarcity of oxytocin-producing neurons in the hypothalamic paraventricular nucleus in PWS has been associated with hyperphagia and obesity. We report the effectiveness very low energy diet (VLED), and treatment with GLP-1 agonist and nasal oxytocin in an immobilized PWS patient with supermorbid-obesity and respiratory failure.

Case Report: A 17-year-old male who had never been treated with growth hormone presented with severe dyspnea and cyanosis. He had chronic obstructive sleep apnea and was receiving home CPAP treatment. At presentation his height, weight, and BMI were 150.3cm (-3.86SDS), 196kg (6.01SDS) and 87.1 kg/m2 (4.96SDS), respectively. His heart-rate was 115 beats/minute, breathing-rate was 48 breaths/minute and body temperature was 36°C. He had limited mobility due to super-obesity. Blood gas was compatible with respiratory acidosis (ph:7,14 CO2:109), fasting blood glucose 110mg/dL, insulin 18mU/L, HbA1c 6.2%, but acute marked elevation of aminotransferases (AST 2357U/L, ALT 2439U/L) were suggestive of hypoxic hepatitis. Due to respiratory failure he received one week of ventilation support in ICU and was then transferred the pediatric ward. He was started on VLED (850 kcal/day, gradually reduced to 650 kcal) with appropriate vitamin and essential nutrient support. Liraglutide therapy was started at a dose of 0,6mg/day, following which aminotransferases reduced to less than five times upper normal limit. On a liraglutide dose of 1,2mg/day his weight decreased to 170 kg(5.3SDS) after two months, BMI reduced to 75.5 kg/m2(4.75SDS) and his mobility increased. Hypoxic hepatitis resolved (AST 50U/L, ALT 29U/L) although hepatosteatosis persisted on ultrasonography. Fasting blood glucose was 79 mg/dL with insulin 27.5 mU/L and HbA1c 4.8%. Nasal oxytocin treatment was added to the combination of VLED and GLP-1 analog treatment for its suggested hyperphagia-reducing effect.

Conclusion: The main treatment approach for PWS in childhood should aim to control obesity and its complications. There are no published definitive recommendations regarding anti-obesity drugs, bariatric surgery is controversial and carries risks in cases with such severe obesity. The appetite of this hyperphagic patient was controlled with Liraglutide and nasal oxytocin, and BMI decreased with VLED. With these interventions, he recovered greater mobility and improved respiratory function.