Monogenic hypertriglyceridemias [7 genes]

Hypertriglyceridemia (HTG), defined as fasting triglyceride levels higher than 180 mg/dl, is a common dyslipidemia associated with a high risk of cardiovascular disease (with some exceptions). It has been described that a 1 mmol/L (39 mg/dL) increase in triglyceride-rich particles (with a genetic etiology) leads to a three-fold increase in risk of ischemic heart disease. Moreover, it is a rare but well-documented cause of pancreatitis associated with a poor prognosis. Risk of pancreatitis increases proportionally to serum triglyceride levels above a certain threshold.

Most HTGs in the adult population have a complex polygenic origin, where the cumulative effect of multiple independent variants (together with non-genetic factors) increases triglyceride levels. However, some rare causes exist for monogenic HTGs that lead to very high triglyceride levels (>885 mg/dL) from an early age, which may remain throughout the individual’s lifespan or normalize during childhood/adolescence. Monogenic HTGs are extremely uncommon and are generally transmitted following an autosomal recessive pattern. Accurately diagnosing these alterations is essential for the correct treatment of patients based on the risk inherent to each HTG.

• Familial chylomicronemia syndrome (FCS) prevalence 1:100,000–1,000,000.
• Transient infantile hypertriglyceridemia prevalence < 1:1,000,000

Genetic testing can confirm a monogenic hypertriglyceridemia diagnosis. Genetic testing is sometimes a requirement for the prescription of drugs aimed at decreasing triglyceride levels in some subtypes of patients. Once a mutation has been identified in the proband, it is essential to initiate family screening taking into account the disease’s inheritance pattern.

The genes selected for this test allow diagnosing monogenic HTGs.

Aimed at patients with a strong suspicion of monogenic HTG.