What is Hypercholesterolemia?

Familial hypercholesterolemia (FH) is also known as familial hyperbetalipoproteinemia. Clinical features are hypercholesterolemia, characteristic xanthomas, and a family history of early-onset cardiovascular disease. FH is the most common hereditary hyperlipidemia in childhood and the most serious of lipid metabolism diseases. It can cause various life-threatening cardiovascular disease complications and is an important risk factor for coronary artery disease. .

Basic Information

nickname: Familial hyperbetalipoproteinemia
English name: familial hypercholesterolemia
Visiting department: Endocrinology

Common causes: Autosomal dominant inheritance
Common symptoms: High blood LDL-C level, yellow tumor, corneal arch, early-onset coronary heart disease

Causes of familial hypercholesterolemia

Familial hypercholesterolemia is a rare autosomal dominant hereditary disease with familial characteristics. The patient's own low-density lipoprotein (LDL) cholesterol value is abnormally high. If homozygous patients have low-density lipoprotein The protein (LDL) cholesterol value is 4-6 times that of normal people, usually LDL-C is 500-1200mg / dL, or even more than 700mg / dL, but triglycerides are normal; it is also prone to cardiovascular disease in early life.

Clinical manifestations of familial hypercholesterolemia

The most characteristic clinical manifestations of this disease are elevated blood LDL-C levels, xanthomas, corneal arches, and early-onset coronary heart disease. Homozygotes have more severe clinical manifestations than heterozygotes. The clinical manifestations of FH patients depend on their genotype, and non-genetic factors also affect them. The relationship between FH genotypes and phenotypes is complicated. Even with the same mutations, even individuals belonging to the same family have large differences in clinical manifestations. In addition, non-genetic factors such as advanced age, men, smoking, and diet can also significantly affect LDL levels and increase the incidence of coronary heart disease.

Hyperlipidemia

The heterozygote plasma cholesterol concentration is usually 2 to 3 times that of normal people, and the homozygote is 6 to 8 times higher than normal people. The former is between 300mg / dL and 400mg / dL, while the latter is between 600mg / dL and 1,200mg / dL. However, some heterozygous patients did not increase LDL-C significantly.

Yellow tumor

Increased plasma LDL-C levels cause cholesterol to settle in other tissues of the body. Those who deposit on the tendon are called tendon yellow tumors, which are more common in the Achilles tendon and extensor tendons of the hand, and are characteristic of FH; nodular yellow tumors are also easy to form under the elbows and knees; As you age, tendon xanthomas are more common.

3. corneal arch

The infiltration of cholesterol into the cornea forms a corneal arch. Homozygotes can appear before the age of 10, and most heterozygotes appear after the age of 30. Corneal arches are also seen in other types of hyperlipidemia.

4. Atherosclerosis

Homozygous FH mostly shows symptoms and signs of coronary heart disease around the age of 10. The descending aorta, abdominal aorta, thoracic aorta, and pulmonary arterial trunk are prone to severe atherosclerosis, and heart valves and endocardial surfaces can also form Yellow tumor plaques, mostly died of cardiovascular disease before the age of 30. Homozygotes lacking the receptor have a worse prognosis. Male heterozygotes can develop coronary heart disease at the age of 30 to 40, and female heterozygotes are about 10 years later than men.

5. Other

FH patients often have recurrent polyarthritis and tenosynovitis, mainly involving the ankle, knee, wrist, and proximal interphalangeal joints, which cannot be inhibited by anti-inflammatory drugs.

Familial Hypercholesterolemia Test

1.B-ultrasound

Cardiovascular changes are most sensitive to examination and follow-up of FH patients. B-mode ultrasound often reveals aortic root sclerosis. Aortic root sclerosis gradually increases, and aortic valve calcification and / or left coronary artery stenosis may occur at the same time.

Coronary angiography

15% of patients had coronary aneurysm-like dilation (referring to the limited or diffuse dilation of the coronary arteries, whose diameter exceeds 1.5 to 2 times that of adjacent normal coronary arteries), while the age and sex matched control group (non-FH coronary heart disease patients Only 2.5% had coronary aneurysm-like expansion. At the same time, it was found that coronary aneurysm-like expansion was negatively correlated with plasma HDL-C levels. Therefore, FH patients were thought to be prone to coronary aneurysm-like diseases.

3. ECG examination.

Familial Hypercholesterolemia Diagnosis

1. A disease-deficient gene has been identified for one of the family members.

2. Young patients with atherosclerosis were found to have high cholesterol.

3. Patients with high cholesterol were found to have tendinous xanthomas.

A gene chip has been developed in China for low-density lipoprotein receptor (LDLR) defects, APOB gene defects, and overexpression of PSCK9 gene. The entire gene can be sequenced to find abnormal positions in five or six thousand bases.

Familial Hypercholesterolemia Treatment

Diet control

Growing children should have as little as 30% of their daily calorie fat. Diet containing hydrolyzed cellulose, fruits and vegetables are good for lowering blood cholesterol.

2. Lipid-lowering drugs

When children's LDL-C exceeds 160 mg / dl (normal <110 mg / dl), careful evaluation is needed. To prevent the risk of cardiovascular disease, medication is necessary. Homozygous familial hypercholesterolemia often requires further treatment when the diet and drug treatment results are not ideal due to genetic defects.

3.LDL separation

Hemodialysis method accelerates the reduction of LDL and improves the xanthomas and cardiovascular lesions of the skin.

4. Liver transplant

Normal liver tissue is transplanted, secreted enzymes play a role in eliminating LDL, and must be taken for life-long immune control agents.

5. Future development of gene therapy.