This fascinating case details the diagnosis and treatment of a very rare cause of an uncommon biochemical presentation: severe hypertriglyceridemia. After excluding important secondary causes (uncontrolled diabetes mellitus or hypothyroidism, alcohol excess, obesity, nephrotic syndrome, oral estrogens, and certain drugs), initial investigation should aim to distinguish familial chylomicronemia syndrome (FCS) from multifactorial chylomicronemia syndrome. Patients with FCS are at particularly high risk of recurrent pancreatitis and specific therapies are available. Moulin et al. (1) proposed a scoring system to aid in the differentiation of the 2 entities. FCS becomes more likely with: persistent severe fasting hypertriglyceridemia, the absence of previous normotriglyceridemia and secondary factors, previous acute pancreatitis, recurrent abdominal pain, lack of history of familial combined hyperlipidemia, no response to lipid-lowering treatment, and young age of onset (1).Once FCS is deemed likely, further investigations can be planned to elucidate its underlying cause. Pathogenic variants in a number of genes can result in FCS. Most patients have biallelic, loss-of-function variants in LPL, the gene encoding lipoprotein lipase (LPL), which is the key enzyme involved in the release of triglyceride from chylomicrons. Non-LPL-FCS is typically due to pathogenic variants in APOC2, APOA5, LMF1, or GPIHBP1 genes (2). It is possible to test LPL activity following the administration of heparin, and patients with LPL-FCS tend to have the lowest function.
Paul Hamilton (Mon,) studied this question.