Familial dysbetalipoproteinemia

Introduction to familial abnormal -lipoproteinemia Familial dysfunction -lipoproteinemia (FD), also known as type III hyperlipoproteinemia, was first described by Gofman in 1954. It was discovered at the time that this disease was mainly characterized by multiple skin lesions at the tendon. The palm line is like a yellow tumor, which was once called a nodular yellow tumor. basic knowledge Proportion of disease: genetic predisposition, the incidence rate is about 0.004%-0.006% Susceptible people: no special people Mode of infection: non-infectious Complications: arteriosclerosis, coronary heart disease, yellow tumor

Familial abnormal -lipoproteinemia etiology

(1) Causes of the disease

It is currently believed that type III hyperlipoproteinemia is caused by multiple factors abnormalities. In addition to the abnormal variation of Apo E, it is often necessary to combine other genetic or environmental factors abnormalities. Due to the abnormality of Apo E, Apo E is involved. Lipoproteins (CM, VLDL and IDL) are metabolically dysfunctional, while other genetic or environmental factors may cause an increase in the synthesis of triacylglycerol-rich lipoproteins, both of which produce significant hyperlipoproteinemia.

(two) pathogenesis

The triglyceride-rich small intestinal lipoprotein (chylomicron) remnant and hepatic lipoprotein (VLDL) remnant are mainly cleared from circulating blood by a receptor-mediated process, in the process, Apo E The key role, when Apo E is mutated, such as Apo E2, can not normally bind to the liver lipoprotein receptor, thus causing the accumulation of Apo E-containing lipoprotein residues in the patient, Havel et al first observed that it will Apo E2 isolated from patients with type III hyperlipoproteinemia forms a complex with phospholipids. The rate of uptake of this complex by LDL receptors is significantly slower, suggesting that Apo E2 is defective by LDL receptor recognition, Wersgraber et al. It was confirmed that the affinity of ApoE2 and LDL receptor in patients with type III hyperlipoproteinemia was only 1% to 2% of that of normal Apo E3. At the same time, Gregg et al also found that Apo E2 was in normal or high in type III. In patients with lipoproteinemia, the rate of clearance is significantly delayed, suggesting that this metabolic disorder is due to a defect in the ligand rather than a defect in the receptor.

Due to the variation of Apo E, the metabolism of lipoproteins containing Apo E may be impaired in the body. The chylomicrons, VLDL and IDL in humans are rich in Apo E, so these kinds of lipoproteins can be metabolized in the body. Disorders, which cause elevated concentrations of chylomicrons, VLDL and IDL in plasma. However, the phenomenon of low LDL concentrations (ie, lower than normal) in patients with type III hyperlipoproteinemia does not seem to explain well, and some may think that Defects in binding of Apo E2 to LDL receptors result in decreased clearance of VLDL particles, which may increase the proportion of VLDL to LDL. Therefore, plasma LDL concentrations in patients with type III hyperlipoproteinemia may increase due to increased production. However, the plasma LDL concentration in patients with type III hyperlipoproteinemia has not increased, but has been significantly lower. There are two possible explanations for this phenomenon. One is that the liver LDL receptors take up chylomicrons and VLDL remnants. Obstruction, the cholesterol content in the liver cells is reduced, and the free cholesterol content is also decreased, so the feedback causes the LDL receptor on the surface of the cell membrane to be up-regulated (ie, the number and activity of LDL receptors) Plus), the liver's ability to take up LDL increases, which in turn lowers the plasma LDL concentration. Another explanation is that LDL is produced by lipolysis of VLDL synthesized by the liver due to reduced LDL production in the body. IDL is transformed, and this process is affected by many factors. Apo E may be a very important factor influencing this transformation process. Some experiments have shown that Apo E participates in the normal VLDL lipolysis process, although the current IDL transformation The process of becoming LDL is not well understood, but there is data suggesting that Apo E mutations can significantly affect this transformation. It has been found that hepatic -VLDL in patients with type III hyperlipoproteinemia plays a role in normal Apo E3. The lower can be converted to LDL, while Apo E2 has no such effect. In addition, it is clinically observed that the low plasma LDL level in patients with -type hyperlipoproteinemia is accompanied by a significant increase in IDL levels, and this interpretation is also supported.

Familial abnormal beta lipoproteinemia prevention

1. At present, there is no specific preventive measure for this disease. It is necessary to strengthen the prevention and treatment personnel's understanding of the disease and understand the harm and serious consequences of the disease.

2. Patients with this disease should take the initiative to receive low-fat and low-carbohydrate diet treatment, and timely use appropriate lipid-lowering drugs to adhere to treatment.

3. Patients should regularly check their blood lipids to maintain normal levels.

4. Actively prevent complications.

Familial abnormal beta lipoproteinemia complications Complications, arteriosclerosis, coronary heart disease, xanthoma

Early onset atherosclerosis may occur, especially peripheral vascular lesions are more common than coronary arteriosclerosis, and the probability of early onset coronary heart disease is also higher (40 males and 50 females); palm-like strips of yellow tumor And other complications.

Familial abnormal -lipoproteinemia symptoms Common symptoms Diabetes atherosclerosis nodules dyslipidemia

About 1% of the population in North America and Europe are Apo E2 carriers, but in fact most Apo E2 carriers do not show hyperlipoproteinemia, and only 2% of Apo E2 carriers have significant high fat. Proteinemia, so that the incidence of type III hyperlipoproteinemia in the population is estimated to be 1 in 500,000, so a certain amount of -VLDL is present in the plasma of Apo E2 carriers.

Age of onset

Type III hyperlipoproteinemia is rare in children and adolescents. Only a few cases have been reported so far. Male patients are more common than females, and the age of onset of male patients is significantly earlier than that of females. Women usually develop after menopause. At the same time, the presence of diabetes or decreased thyroid function can also make the age of onset of the disease advanced.

2. Yellow tumor

Patients with type III hyperlipoproteinemia often have a variety of cutaneous yellow tumors. Because some xanthoma does not appear in other types of hyperlipoproteinemia, it has certain clinical diagnostic significance, the most characteristic of which is Xanthoma striata palmaris, a yellow lipid deposit in the palmar folds of the palm, about half of the untreated type III hyperlipoproteinemia patients, and Other types of xanthoma can be seen, for example, nodular or nodular rash yellow tumors, nodular yellow tumors often located at the elbow, knee and knuckles, but this yellow tumor is not a type III hyperlipoproteinemia Specifically, macular tumors and tendon yellow tumors are sometimes seen, but tendon yellow tumors are more common in familial hypercholesterolemia.

3. Early onset atherosclerosis

Early onset or accelerated atherosclerosis is seen in 1/3 to 1/2 patients with type III hyperlipoproteinemia. Atherosclerotic lesions occur in the blood vessels around the lower extremities as are common in coronary arteries. There is a significant difference in the location of vascular involvement in familial hypercholesterolemia. The latter's lower extremity vascular involvement is rare. Why is it easy to combine vascular atherosclerosis in lower limbs with type III hyperlipoproteinemia? The mechanism is not very clear. In the cholesterol-fed animal model, it was observed that when the plasma -VLDL concentration was significantly increased, the combined peripheral atherosclerosis was more common than coronary atherosclerosis, suggesting that patients with type III hyperlipoproteinemia are likely to merge around. Vascular lesions may be associated with a significant increase in plasma -VLDL concentration.

In a large number of patients with type III hyperlipoproteinemia, 43% of patients had peripheral vascular disease, about 1/3 of patients had established coronary heart disease, and the age of male patients with vascular involvement ( The average age of 40 years old is earlier than that of female patients (average 50 years old). It is generally believed that if the plasma cholesterol level is significantly elevated in patients with type III hyperlipoproteinemia, the risk of developing atherosclerosis is high.

Recently, 93 patients with type III hyperlipidemia were analyzed for atherosclerosis of the external carotid artery, coronary artery and peripheral arteries to evaluate the frequency and relationship of atherosclerosis in different sites. Those with sclerosis accounted for 13%, those with coronary artery disease accounted for 22%, and those with peripheral atherosclerotic lesions accounted for 27%, but those with lesions at three sites were rare.

4. Accompanying disease

Some systemic diseases are often associated with type III hyperlipoproteinemia and may aggravate type III hyperlipoproteinemia. Nearly 1/2 of patients with type III hyperlipoproteinemia have elevated plasma uric acid levels, but most patients Asymptomatic, only 4% of patients have clinical gout, and type III hyperlipoproteinemia is associated with impaired glucose tolerance. However, there are few cases of diabetes, and thyroid dysfunction exists in combination with this disease. It will aggravate its dyslipidemia. On the contrary, hyperthyroidism can alleviate dyslipidemia and even make hyperlipidemia disappear.

Examination of familial abnormal beta lipoproteinemia

1. VLDL-cholesterol/plasma triacylglycerol ratio

This ratio 0.3 (mg / mg) has almost diagnostic significance for type III hyperlipoproteinemia; and the ratio 0.28 (mg / mg) suggests that type III hyperlipoproteinemia may be.

2. VLDL-cholesterol/VLDL-triacylglycerol ratio

This ratio 1.0 (mmol/mmol) is valuable for the diagnosis of type III hyperlipoproteinemia.

3. Plasma cholesterol and triglyceride concentrations are significantly increased, plasma cholesterol concentration is usually higher than 7.77mmol / L (300mg / dl), can be as high as 26.0mmol / L, the degree of plasma triglyceride increased (if in mg /dl is a unit that is roughly equal or higher than plasma cholesterol levels.

4. Plasma LDL is reduced, HDL is normal or slightly reduced.

5. -VLDL showing -mobility in plasma electrophoresis.

6. The most reliable biochemical marker for the diagnosis of type III hyperlipoproteinemia is the determination of the Apo E phenotype or the Apo E genotype.

There is currently no relevant information.

Diagnosis and identification of familial abnormal -lipoproteinemia

Diagnostic criteria

There is currently no simple and reliable method for diagnosing type III hyperlipoproteinemia in clinical practice, but some features may suggest and support the diagnosis of this disease.

1. Palmaroma or nodular xanthoma without hepatic disease; however, not every type III hyperlipoproteinemia can be found in yellow tumors, and the yellow tumor in the palm area can almost establish the diagnosis of this disease, while others Types of xanthoma are not unique to this disease and can be found in other types of hyperlipoproteinemia.

2. Plasma cholesterol concentration and triacylglycerol concentration are significantly increased and the degree is equivalent (for example, are close to 400mg / dl), should think of type III hyperlipoproteinemia, once thought that type III hyperlipoproteinemia patients Plasma cholesterol and triglyceride concentrations fluctuate widely, but recent studies have shown that there is no significant characteristic of fluctuations in blood lipid levels in patients with this condition.

3. Plasma -VLDL is considered to be the main basis for the diagnosis of type III hyperlipoproteinemia. VLDL in plasma is rich in cholesterol ester (more than 25%, normal is about 15%) is one of the characteristics of -VLDL. Generally, the degree of cholesterol-containing ester in VLDL can be reflected by measuring two ratios: 1 VLDL-cholesterol/plasma triglyceride ratio, which is 0.3 (mg/mg), which is almost diagnosed for type III hyperlipoproteinemia. Significance; and the ratio 0.28 (mg/mg) suggests that it may be type III hyperlipoproteinemia, 2VLDL-cholesterol/VLDL-triacylglycerol ratio, the ratio 1.0 (mmol/mmol) for the diagnosis of type III hyperlipoproteinemia The disease is very valuable.

4. When plasma was subjected to agarose electrophoresis, it was confirmed that there was a wide band, which supports the diagnosis of type III hyperlipoproteinemia, but it is not very reliable. If ultracentrifugation can be used to separate VLDL, VLDL is subjected to agarose electrophoresis. If VLDL moves to the -position, the diagnostic value of type III hyperlipoproteinemia is greater.

5. The most reliable biochemical marker for the diagnosis of type III hyperlipoproteinemia is the determination of the Apo E phenotype or the Apo E genotype.

Apo E2 is present at the same time as any of the above features to establish a diagnosis of type III hyperlipoproteinemia. The phenotype or genotype of Apo E is not altered by other factors.

Differential diagnosis

Identification with familial hypercholesterolemia, familial hypertriglyceridemia, familial mixed hyperlipidemia, etc., as shown in Table 2.

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