Related Experiment Video
Updated: Jun 4, 2026
Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Clinical presentation, laboratory values, and coronary heart disease risk in marked high-density
Raul D Santos1, Bela F Asztalos, Lilton R C Martinez
1Lipid Clinic, Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
Insights
Diagnosing inherited high-density lipoprotein (HDL) deficiency involves identifying specific apolipoprotein A-I (ApoA-I) levels and mutations. These conditions, particularly ApoA-I deficiencies, are strongly linked to premature coronary heart disease (CHD) risk.
Area of Science:
- Lipid metabolism and cardiovascular genetics
- Inherited dyslipidemias
- Coronary heart disease risk factors
Background:
- Marked high-density lipoprotein (HDL) deficiency, defined as HDL cholesterol levels below 10 mg/dL, presents diagnostic challenges.
- Severe HDL deficiency can occur in the absence of severe hypertriglyceridemia or liver disease.
- Understanding the genetic basis and clinical implications of HDL deficiency is crucial for risk assessment.
Purpose of the Study:
- To establish a diagnostic framework for inherited causes of severe HDL deficiency.
- To elucidate the association between severe HDL deficiency and coronary heart disease (CHD) risk.
- To review and categorize different forms of severe HDL deficiency based on plasma apolipoprotein (Apo) A-I levels and associated clinical features.
Main Methods:
- Systematic review of published literature on severe HDL deficiencies.
- Classification of deficiency types based on plasma apolipoprotein (Apo) A-I presence and concentration.
- Correlation of specific genetic defects (e.g., ABCA1 gene mutations, lecithin:cholesterol acyltransferase deficiency) with clinical manifestations and CHD risk.
Main Results:
- Three forms of ApoA-I deficiency (without plasma ApoA-I) are associated with premature CHD: ApoA-I/C-III/A-IV deficiency, ApoA-I/C-III deficiency, and ApoA-I deficiency.
- Tangier disease, characterized by low plasma ApoA-I (<10 mg/dL) and ABCA1 gene mutations, is linked to premature CHD, peripheral neuropathy, and specific cellular lipid accumulation.
- Lecithin:cholesterol acyltransferase deficiency presents with low ApoA-I (<40 mg/dL), altered cholesterol esterification, corneal opacification, splenomegaly, and renal failure risk, but not clearly premature CHD.
Conclusions:
- Inherited severe HDL deficiency has diverse etiologies, including ApoA-I deficiencies and Tangier disease.
- Most forms of severe HDL deficiency, particularly those involving ApoA-I absence or severe reduction, are associated with an increased risk of premature coronary heart disease.
- A structured diagnostic approach is necessary to identify the specific cause of severe HDL deficiency and manage associated cardiovascular risks.
Abstract:
Our purpose is to provide a framework for diagnosing the inherited causes of marked high-density lipoprotein (HDL) deficiency (HDL cholesterol levels <10 mg/dL in the absence of severe hypertriglyceridemia or liver disease) and to provide information about coronary heart disease (CHD) risk for such cases. Published articles in the literature on severe HDL deficiencies were used as sources. If apolipoprotein (Apo) A-I is not present in plasma, then three forms of ApoA-I deficiency, all with premature CHD,and normal low-density lipoprotein (LDL) cholesterol levels have been described: ApoA-I/C-III/A-IV deficiency with fat malabsorption, ApoA-I/C-III deficiency with planar xanthomas, and ApoA-I deficiency with planar and tubero-eruptive xanthomas (pictured in this review for the first time). If ApoA-I is present in plasma at a concentration <10 mg/dL, with LDL cholesterol that is about 50% of normal and mild hypertriglyceridemia, a possible diagnosis is Tangier disease due to mutations at the adenosine triphosphate binding cassette protein A1 (ABCA1) gene locus. These patients may develop premature CHD and peripheral neuropathy, and have evidence of cholesteryl ester-laden macrophages in their liver, spleen, tonsils, and Schwann cells, as well as other tissues. The third form of severe HDL deficiency is characterized by plasma ApoA-I levels <40 mg/dL, moderate hypertriglyceridemia, and decreased LDL cholesterol, and the finding that most of the cholesterol in plasma is in the free rather than the esterified form, due to a deficiency in lecithin:cholesterol acyltransferase activity. These patients have marked corneal opacification and splenomegaly, and are at increased risk of developing renal failure, but have no clear evidence of premature CHD. Marked HDL deficiency has different etiologies and is generally associated with early CHD risk.
Related Concept Videos
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:26Coronary Artery Disease IV: Preventive Measures
01:30Coronary Artery Disease III: Clinical Manifestations
01:30Coronary Artery Disease I: Introduction
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:30Acute Coronary Syndrome III: Diagnostic Studies