Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder of
chylomicron metabolism causing severe elevation of
triglyceride (TG) levels (>10 mmol L-1 ). This condition is associated with a significant risk of recurrent
acute pancreatitis (AP). AP caused by hypertriglyceridaemia (HTG) has been associated with a worse prognosis and higher mortality rates compared to
pancreatitis of other aetiology. Despite its association with poor quality of life and increased lifelong risk of HTG-AP, few healthcare providers are familiar with FCS. Because this condition is under-recognized, the majority of FCS patients are diagnosed after age 20 often after consulting several physicians. Although other forms of severe HTG such as multifactorial chylomicronemia have been associated with high atherosclerotic
cardiovascular disease (ASCVD) risk and metabolic abnormalities, ASCVD and
metabolic syndrome are not usually observed in FCS patients. Because FCS is a genetic condition, the optimal diagnosis strategy remains genetic testing. The presence of bi-allelic pathogenic mutations in LPL,
APOC2, GPIHBP1, APOA5 or LMF1 genes confirms the diagnosis. However, some cases of FCS caused by
autoantibodies against LPL or GPIHBP1
proteins have also been reported. Furthermore, a clinical score for the diagnosis of FCS has been proposed but needs further validation. Available treatment options to lower
triglycerides such as
fibrates or
omega-3 fatty acids are not efficacious in FCS patients. Currently, the cornerstone of treatment remains a lifelong very
low-fat diet, which prevents the formation of
chylomicrons. Finally, inhibitors of
apo C-III and ANGPTL3 are in development and may eventually constitute additional treatment options for FCS patients.