Monogenetic severe hypertriglyceridemia: Familial chylomicronemia syndrome
Familial chylomicronemia syndrome (FCS) is a rare genetic disorder of lipid metabolism which leads to severely raised triglyceride levels (>10 mmol/L; >885 mg/dl) and chylomicrons (chylomicronemia). This can result in debilitating signs and symptoms including severe abdominal pain and acute pancreatitis.1 The syndrome occurs in only 1 per million individuals.2
Familial chylomicronemia also known as:
Type I hyperlipoproteinemia, lipoprotein lipase (LPL) deficiency, or monogenic chylomicronemia.3
Red Flags of FCS
- Triglyceride leves >10 mmol/l or 885 mg/dl
- Acute or chronic pancreatitis
High triglyceride levels, the hallmark of FCS, results from low LPL activity. LPL is an enzyme that breaks down triglycerides in chylomicrons circulating in the bloodstream.4
Because of their extremely high triglyceride levels, patients with FCS are at a high risk of recurrent acute pancreatitis, compared with pancreatitis of other aetiologies, hypertiglyceridemic pancreatitis is associated with higher mortality and:5,6,7
Higher rates of persistent organ failure
(40% vs 17%)
Longer hospital stays
(10 days vs 7 days)
Increased admission to intensive care units
(45% vs 23%)
FCS is often underdiagnosed
FCS is underdiagnosed, despite pediatric onset, FCS is typically diagnosed in patients over 20 years of age, usually after numerous consultations at different healthcare providers.8
References
- Moulin P, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an ”FCS score”. Atherosclerosis. 2018;275:265–272.
- Brahm AJ, Hegele RA, Chylomicronaemiadcurrent diagnosis and future therapies, Nat. Rev. Endocrinol. 11 (6) (2015) 352e362.
- Gotoda T, et al., Diagnosis and management of type I and type V hyperlipoproteinemia, J. Atherosclerosis Thromb. 19 (1) (2012) 1e12.
- Bashir B, et al. Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome—Causes, Clinical Presentation, and Therapeutic Options. Metabolites 2023, 13, 621.
- Nawaz H, et al. Am J Gastroenterol 2015; 110 (10): 1497-1503. doi: 10.1038/ajg.2015.261.
- Deng LH, et al. World J Gastroenterol 2008; 14 (28): 4558-4561. doi: 10.3748/wjg.14.4558. PMID:18680239.
- Wang Q, et al. J Clin Gastroenterol 2017; 51 (7): 586-593. doi: 10.1097/MCG.0000000000000846.
- Baass A, et al. Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia (Review). J Intern Med 2020; 287: 340–348.
Causes and Pathophysiology
FCS is a monogenic disease with different pattern of inheritance. In 80-90% of patients with FCS, low activity of lipoprotein lipase (LPL) is caused by mutations in the gene that encodes this enzyme.
Symptoms and complications
Learn more about the broad spectrum of signs and symptoms that are associated with FCS.
Diagnosis
FCS diagnosis is based on a three-step approach:
- High triglyceride evaluation
- Identification of candidates for FCS genetic testing
- Genetic test of possible affected genes