A Case of Early-Onset Severe Hypertriglyceridemia Found with Monogenic Chylomicronemia During Adulthood

Severe hypertriglyceridemia is defined as a serum triglyceride (TG) level above 1000mg/dL. Compared with moderate hypertriglyceridemia, which is more common, severe hypertriglyceridemia is present in 0.4% of general population. The latter owns a risk of recurrent pancreatitis, and the need of intensive care unit and mortality is higher compared to cases of pancreatitis with normal TG levels. Evaluation of severe hypertriglyceridemia should consist of assessment of underlying conditions and consideration of genetic testing for lipoprotein lipase (LPL) and its regulating genes.

Case Description :

A 45-year-old woman was referred by her Endocrinologist to the Lipid Clinic. She has a history of severe hypertriglyceridemia since 6-month-old, primary hypothyroidism, and breast cancer on remission. Patient had developed four episodes of pancreatitis, which occurred during her pregnancies. She reported highest TG level has been 5315mg/dL. Pharmacotherapy consisted of fenofibrate, prescribed omega-3 (combined eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), pioglitazone, levothyroxine, and had started orlistat one week ago. Patient had no personal or family history of premature atherosclerotic cardiovascular disease. She denied alcohol use. Patient is followed by a nutritionist for a low-fat diet but admits inconsistent adherence. Physical examination revealed an underweight woman without xanthomas. Lipid profile showed TG level 1204mg/dL, high-density lipoprotein 11mg/dL and total cholesterol 177mg/dL. Thyroid function tests were within normal limits. A comprehensive analysis for genes associated to inherited lipidemia was performed, subsequently revealing two pathogenic variants in LPL gene (c.644G >A [p. Gly215Glu]) consistent with homozygous autosomal recessive familial chylomicronemia syndrome (FCS). Orlistat was discontinued as patient did not tolerate gastrointestinal effects and low-fat diet was reinforced. As patient continued to lose weight with this diet, medium-chain TG oil supplement was started to increase calories. Patient has remained with stable TG levels but has failed to achieve the clinical goal (less than 1000mg/dL) with available therapies.

Discussion :

FCS is a rare genetic disorder characterized by severe hypertriglyceridemia due to reduced LPL activity. These cases are generally unresponsive to TG-lowering medications as most available therapies involve LPL in their mechanism. FCS places a burden in these patients resulting in a diminished quality of life, employment opportunities, social relationships, and emotional well-being. There is need for greater disease awareness, improved clinical diagnosis, and more effective treatment options for FCS.