Endocrine Abstracts

Introduction: Familial chylomicronemia syndrome (FCS) is a rare inherited disorder of lipoprotein metabolism leading to severe hypertriglyceridemia and increased risk for acute pancreatitis. Mutations in the lipoprotein lipase (LPL) gene account for the majority of cases of monogenic chylomicronemia.

Methods: We report the cases of two white males with a novel homozygous mutation in position 332 of the LPL gene.

Results: The patients are siblings from a consanguineous marriage and presented the same homozygous mutation in the LPL gene identified as c.995C>G [p.(Thr332Ser)]. This variant has not been previously described and was deemed a variant of uncertain significance (VUS). According to the clinical manifestations and genetic findings on both patients, the diagnosis of FCS was established. Both patients were diagnosed during childhood at 14-years-old with severe hypertriglyceridemia and have a previous history of recurrent acute pancreatitis (8 episodes in one sibling and 2 episodes in the other). One patient developed diabetes mellitus secondary to pancreatic disease. Dietary modification plays a key role on management of FCS and severe restriction of dietary fat to <20 grams per day is recommended. Therapeutic resistance to routine triglyceride-lowering medication is a hallmark of FCS and the patients currently have triglyceride levels ranging from 1217-2920 mg/dl, under fenofibrate and omega-3 fatty acids therapy. Treatment with apolipoprotein C-III inhibitor volanesorsen is under consideration.

Conclusions: We describe a novel LPL mutation related to familial chylomicronemia syndrome. Even though it was considered a variant of uncertain significance in light of current knowledge, the mutation appears to be pathogenic according to clinical characteristics, causing severe hypertriglyceridemia with increased risk of acute relapsing pancreatitis.