Familial hypertriglyceridemia (FHTG) is an autosomal dominant disorder with an estimated prevalence of 1 in 300-400 in the general population. The prevalence of this disorder is estimated to be 1 in 300-400 in the general population, and plasma triglyceride levels are typically 3.4-9.0 mmol/L (300-800 mg/dl). Another characteristic of FHTG patients is that plasma LDL-C and HDL-C levels are lower than the average of the general population. Yunfei Wang, Cardiovascular Disease Specialist, Guangdong Provincial Hospital of Traditional Chinese Medicine
In childhood, patients with FHTG do not show hypertriglyceridemia, suggesting that the development of FHTG is related to the role of certain environmental factors in addition to a genetic defect. To date, the molecular pathological basis of FHTG is not clear. Studies using isotope labeling methods have shown that many patients with FHTG have excessive production of VLDL-triglycerides, while Apo B100 production may be normal or mildly increased. Since each lipoprotein particle contains only one Apo B100 molecule, the newly secreted VLDL particles in the liver of FHTG patients contain more triglycerides than normal. The results of in vivo studies on VLDL metabolism suggest that only a small proportion of VLDL in these patients is converted to LDL, which may partially explain the lower than normal plasma LDL levels in FHTG patients. However, it has also been suggested that LDL clearance is significantly greater in these patients than in normal controls. This phenomenon may also be the main reason for the low LDL levels. At the same time, Apo AI synthesis is also reduced in patients, resulting in hypoHDL-Cemia.
In patients with severe hypertriglyceridemia, celiac disease may also be present in fasting plasma, and plasma triglyceride concentrations may be as high as 56 mmol/L (5000 mg/dl) or even higher. In some families, two or more members may have significantly elevated plasma triglyceride levels, suggesting that there may be a unique genetic defect or a combination of other genetic defects that interfere with triglyceride metabolism in the family. The latter may be more common, as patients with FHTG often have a combination of obesity, hyperuricemia, and abnormal glucose tolerance. In patients with moderate hypertriglyceridemia combined with diabetes mellitus, there is a significant increase in plasma VLDL and fasting celiac disease.
Mild to moderate hypertriglyceridemia often has no specific signs or symptoms. If plasma triglyceride concentrations reach 11.3 mmol/L (1000 mg/dL) or higher, splenomegaly with fat accumulation in macrophages and hepatocytes is often observed. Rash-like yellow tumors may appear on the skin of the trunk and proximal extremities (Figures 18 and 19), as well as on the distal extremities. The main risk of hypertriglyceridemia is the predisposition to acute hemorrhagic pancreatitis, which is directly related to the concentration of celiac particles in the plasma; presumably due to acute obstruction of blood flow to the microvasculature of the pancreas by celiac emboli. This hypothesis is somewhat convincing because other systems may occasionally show functional abnormalities, such as transient cerebral dysfunction, sensory abnormalities in the extremities, dyspnea, and intestinal dysfunction in the form of abdominal pain and diarrhea. These abnormalities can be alleviated by lowering the plasma concentration of celiac particles.
To date, there is no direct evidence that elevated VLDL and celiac concentrations cause atherosclerotic lesions in FHTG, but a growing body of research suggests that hypertriglyceridemia is a risk factor for coronary heart disease. Therefore, patients with FHTG should be treated with lipid-lowering therapy, especially in patients with severely elevated plasma triglyceride levels, and triglyceride-lowering therapy should be more aggressive, because it is beneficial to prevent the occurrence of acute pancreatitis. Commonly used lipid-lowering drugs include fibrates, cellofibrates and fish oil.