Familial Chylomicronaemia Syndrome (FCS) Compared to Multifactorial Chylomicronaemia Syndrome (MCS) – Lessons Learnt from United Kingdom FCS Registry

Background and Aims: FCS is a rare autosomal recessive disorder. Its natural history is not fully understood. The aim of the study is to investigate the natural history of FCS, genotype-phenotype correlation and to explore the differences between FCS and MCS. Methods: While data collection is ongoing, we performed an initial analysis of baseline characteristics of 103 patients (FCS: 50, MCS:53) from the UK FCS database. Results: FCS was prevalent in individuals of Asian ethnicity with history of parental consanguinity (p=<0.001 for both). LPL mutations were most prevalent, however its prevalence varied depending on ethnic background (Caucasians 78.9%, Asians: 51.6%). FCS patients had higher prevalence of acute pancreatitis (80% vs 54.7%, p=0.006), recurrent pancreatitis (70% vs 37.7%, p=0.001), unexplained abdominal pain (84% vs 43.4%, p=<0.001), earlier age (years) of symptom onset [19.6 (6.9 – 30.2) vs 34.5 (26.0 – 42.0), p=<0.001] and acute pancreatitis [24.8 (12) vs 32.2 (13.8), p=0.02]. BMI (kg/m2) of FCS cohort was lower [24.6 (20.3 – 27.0) vs 28.1 (25.4 - 31.9), p= <0.001]. Obesity, clustering of metabolic features (diabetes, hypertension, obesity), and ASCVD was less prevalent in FCS (p=0.002, 0.001 & 0.09 respectively). No difference in the disease burden between LPL mutation-FCS and non-LPL mutations-FCS. Phenotype of patients with one pathogenic variant was intermediate between homozygous and no pathogenic variants. Conclusions: FCS patients have significantly higher risk of pancreatic complications. Prevalence of diabetes, hypertension, obesity is less compared to MCS. LPL FCS and non-LPL FCS are phenotypically similar. Carriers of one pathogenic variant have an intermediate phenotype.