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Dyslipoproteinemias

Dyslipoproteinaemia

For medical students2 min readUpdated 2026-10-10

Dyslipoproteinemia is a standard pathological form of lipid metabolism characterized by abnormal levels, structures, and ratios of various lipoproteins in the blood. Disruptions in their metabolism are a central link in the pathogenesis of atherosclerosis, pancreatitis, and tissue ischemia.

HLP Types5 main types identified according to the Fredrickson classification

Atherogenic IndexNormal cholesterol atherogenic index (AI) is $\le 3.0$

Synthesis OrganThe liver plays a key role in cholesterol transport and clearance

AcanthocytesSpur cells (erythrocytes with spiked projections) seen in abetalipoproteinemia

Classification and Types of Hyperlipoproteinemias

The historical classification was developed in 1967 by Fredrickson and colleagues, and later revised by WHO experts. It is based on plasma levels of total cholesterol and triglycerides, as well as the distribution of lipoprotein fractions using electrophoresis and ultracentrifugation. There are 5 main types of disorders.

Depending on their ability to induce vascular pathology, lipoproteins are divided into two groups:

Atherogenic (promote atherosclerosis): VLDL, LDL, and IDL.
Anti-atherogenic (protect against pathology): HDL.

The anti-atherogenic effect of HDL is achieved through reverse cholesterol transport from cell membranes to the liver, as well as via high concentrations of apoE, which allows them to compete with LDL for cellular receptors.

Evaluation of Blood Atherogenicity

To assess the risk of cardiovascular events, the cholesterol atherogenic index (AI) is used. It is calculated by the formula:

$$AI = \frac{\text{Total Cholesterol} - \text{HDL Cholesterol}}{\text{HDL Cholesterol}}$$

Norm: Values are $\le 3.0$.
Pathology: When the index rises above 3.0, the risk of atherosclerosis increases sharply.

Three groups of factors influence the course and clinical presentation of these disorders: hereditary metabolic traits, environmental factors (dietary habits and lifestyle), and comorbid conditions such as obesity, hypothyroidism, diabetes mellitus, or liver disease.

Secondary Forms and Inherited Disorders

Secondary disorders develop secondary to other diseases. For example, in diabetes mellitus, lipoprotein lipase activity drops and VLDL synthesis increases, while chronic alcoholism causes similar enzyme inhibition and increased lipoprotein synthesis.

Among inherited combined forms, abetalipoproteinemia is associated with a mutation in the apoB gene. In this condition, beta-lipoproteins, chylomicrons, LDL, and VLDL are completely absent from the blood. This leads to severe consequences:

Appearance of acanthocytes—erythrocytes with spiked projections.
Vitamin E and A deficiency due to impaired transport.
Steatorrhea and impaired fat absorption in the gastrointestinal tract.
Axonal demyelination of the nervous system, leading to ataxia.

Mnemonic

AI = (Total Cholesterol minus HDL) divided by HDL. Normal is up to 3.0 — anything above 3 leads to atherosclerosis.

Frequently asked questions

What types of hyperlipoproteinemia are distinguished by the Fredrickson classification?

According to the Fredrickson classification, there are 5 main types of hyperlipoproteinemias. They differ in total cholesterol, triglycerides, and lipoprotein fraction distribution:

Type I (includes variants IA and IB);
Type II (characteristic of familial hypercholesterolemia);
Type III (familial combined hyperlipidemia, associated with impaired clearance of remnant lipoproteins);
Type IV (familial hypertriglyceridemia);
Type V (familial mixed hypertriglyceridemia).

Hereditary defects and acquired diseases (e.g., diabetes mellitus, nephrotic syndrome) can lead to various types of dyslipoproteinemia.

Which enzymes participate in plasma lipoprotein metabolism?

Key enzymes associated with lipoprotein metabolism include:

Lecithin-cholesterol acyltransferase (LCAT);
Hepatic lipase (HL);
Lipoprotein lipase (LPL, including blood lipoprotein lipase).

Lipoprotein lipase has high clinical significance: decreased activity is observed in diabetes mellitus and chronic alcoholism as a mechanism of secondary lipid metabolism disorders. Activation of blood lipoprotein lipase is cited as an example of metabolic correction in hypercholesterolemia.

Through which receptors do cells uptake LDL?

Cellular uptake of low-density lipoproteins occurs primarily via specialized LDL receptors.

LDL receptors provide the main pathway for particle uptake via endocytosis. These receptors selectively recognize apolipoproteins apoB-100 and apoE present on the surface of LDL particles.

Mutations in the LDL receptor gene impair its endocytosis capability after binding to lipoproteins. This receptor structural defect leads to familial hypercholesterolemia and premature atherosclerosis.

Which lipoproteins are considered atherogenic?

Atherogenic fractions include very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL).

What is the protective mechanism of HDL?

HDL perform reverse transport of excess cholesterol from cells to the liver for excretion in bile, and they also compete with LDL for receptors due to their high apoE content.

What are the main manifestations of abetalipoproteinemia?

The pathology manifests as the absence of beta-lipoproteins and chylomicrons in the blood, the appearance of acanthocytes, steatorrhea, fat-soluble vitamin deficiency, and axonal demyelination of the nervous system.

Go deeper

History of the Fredrickson classification and the ultracentrifugation method
Detailed analysis of chylomicron remnant distribution across HLP types
Molecular mechanisms of Tangier disease and foam cell accumulation
Effects of hypothyroidism and nephrotic syndrome on lipid catabolism
Nervous system and visual pathway disorders in apoB deficiency