Characterizing familial chylomicronemia syndrome: Baseline data of the APPROACH study.

Abstract

Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder caused by mutations in lipoprotein lipase (LPL) or genes required for LPL functionality and is characterized by hyperchylomicronemia that results in recurrent episodes of acute pancreatitis. Owing to the rarity of FCS, there are few case series describing the phenotypic variability in FCS patients in detail. To provide baseline characteristics in the largest study population to date of patients with FCS. We analyzed baseline demographic and clinical characteristics of adult FCS patients in the phase 3 APPROACH study of volanesorsen sodium (antisense inhibitor of apolipoprotein C-III). Sixty-six patients were included in the analysis. Mean (SD) age was 46 (13) years; and mean body mass index was 24.9 (5.7) kg/m2. We identified causal mutations in 79% (52) of patients, with LPL mutations accounting for 62% (41) of cases. Median age at diagnosis was 24 years, 54% were females, and 81% were Caucasian. All patients followed a low-fat diet, 43% received fibrates, 27% fish oils, and 21% statins. Median fasting triglyceride levels (P25, P75) were 1985 (1179, 3047 mg/dL). Overall, 76% of patients reported ≥1 lifetime episode of acute pancreatitis; 23 patients reported a total of 53 pancreatitis events in the 5 years before enrollment. Our data emphasize the severe hypertriglyceridemia characteristic of FCS patients despite restrictive low-fat diets and frequent use of existing hypolipemic therapies. Acute pancreatitis and recurrent acute pancreatitis are frequent complications of FCS. Diagnosis at an older age suggests likely underdiagnosis and underappreciation of this rare disorder.