Severe hypertriglyceridemia leads to chylomicronemia resulting in various symptoms
Monogenetic severe HTG, familial chylomicronemia syndrome, has a broad spectrum of signs and symptoms:1
Physical:
Digestion:
- Bloating*
- Indigestion*
- Lack of appetite
- Flatulence
- Nausea/vomiting
- Steotorrhea
Skin:
- Eruptive xanthomas
- Skin changes resembling sunburn
- Excessive sweating
- Cold sensations
Extermities:
- Cold extremities
- Numbness or tingling of digits
Sites of pain:
- Generalized abdominal pain
- Back pain
- Pancreatic pain
- Joint pain
- Headaches
Energy:
- Asthenia*
- Fatigue*
Other:
- Jaundice
- Respiratory problems/dyspnea
Emotional:
Uncertainty about:
- The possibility of an attack of acute pancreatitis or pain† at any time
- Diet
Anxiety/fear/worry surrounding:
- Health†
- Social situations
- FCS testing schedule
Feeling:
- Out of control/helpless†
- Sad/down/depressed
- Anger/frustration about having FCS
- Misunderstood
- Social withdrawal/isolation
Cognitive:
- Difficulty concentrating‡
- Impaired judgment‡
- Brain fog‡
- Forgetfulness‡
- Comprehension difficulties
- Recent memory loss
- Difficulty hearing
Severe and persistent hypertriglyceridemia
(>10mmol/l; >885 mg/dl) increases the risk of:
Acute pancreatitis associated with:2
- High mortality
- Higher rates of persistent organ failure
- Longer hospital stays
- Increased admission to intensive care units
in comparison with normal triglyceride levels
Chronic pancreatitis which can lead to:3
- Pancreatic failure in both exocrine and endocrine function, with the occurrence of diabetes
Mild-to-moderate HTG* is associated with high risk of acute pancreatitis in the general population5
Risk of acute pancreatitis by increasing triglycerides level: prospective cohort study (N=116, 550) (median follow-up 6.7 years)
*≥177 mg/dL (≥2mmol/L)
Adjusted for age, sex, and baselune markers of lifestyle and known risk factors for pancreatitis (ie, for education smoking, hypertension, statin use, study cohort, and birth year) CI, confidence interval; HR, hazard ratio; HTG, hypertriglyceridaemia
References
- Davidson M, et al. The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study. J Clin Lipidol 2018;12(4):898–907.
- Nawaz H, et al. Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. Am J Gastroenterol. 2015;110:1497-503.
- Gaudet D et al., Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency Atherosclerosis Supplements 11 (2010) 55–60
- 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.
- Pedersen SB et al. Nonfasting Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis. JAMA Intern Med 2016;176:1834–42
Management
FCS management includes dietary control, pharmacological treatment, and treatment of acute pancreatitis.
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
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.