De Gier_2022_Atherosclerosis_355_65

Background and Aims : FCS is an extremely rare genetic disease resulting in severe chylomicronaemia and high risk of recurrent pancreatitis in early childhood. Genes causing the disease include LPL, APOA5, APOC2, LMF1, and GPIHBP1. Methods: We report the case of a 19-year-old with FCS caused by a homozygous c.337T>C (p.Trp113Arg) mutation in the LPL gene. Results: The patient was diagnosed at the age of two months showing plasma triglyceride levels above 30.000 mg/dL. The treatment consisted of a restricted low-fat diet supplemented with medium-chain triglycerides. Medical initiatives with fibrates and omega-3-fatty-acids showed no effect. Due to severe hypertriglyceridemia, the patient suffered from acute pancreatitis at the age of six. To prevent comorbidities, the patients family established an extreme activity program resulting in intense training sessions as a professional handball player. At the age of 18 years, we started pharmacotherapy with Volanesorsen, an Apo-C-III inhibitor, that is approved for adult patients with FCS and risk of pancreatitis, with subcutaneous (s.c.) injections of Volanesorsen 285 mg weekly. After 8 weeks, triglycerides declined significantly up to -85%. Nevertheless, the triglyceride levels were volatile, ranging from 295 to 4400 mg/dL. The overall mean reduction was -20%. There was a significant correlation with dietetic incompliance during extreme physical activity and training camps. As known side effect, thrombocytes decreased persistently <140 G/L after 18 weeks of therapy. After recovery of thrombocytopenia during a five-week pause, a biweekly s.c.-injection was continued. Conclusions: Significant correlations with diet incompliance were observed and indicate the need for continued restriction of fat intake during therapy with Volanesorsen.