cholesterol-ester transfer protein deficiency

Cholesterol-Ester Transfer Protein (CETP) Deficiency: An Overview

CETP deficiency is a rare genetic condition characterized by the inability to properly transfer cholesteryl esters between lipoproteins in the bloodstream. This leads to an imbalance in lipid profiles, resulting in increased levels of High-Density Lipoprotein (HDL) cholesterol and decreased levels of Low-Density Lipoprotein (LDL) cholesterol.

Key Features:

• Increased HDL cholesterol levels [1][2]
• Decreased LDL cholesterol levels [3][4]
• Typically antiatherogenic profile, meaning it reduces the risk of atherosclerosis [5]
• Heterozygous individuals have 60-70% of normal CETP activity and only a modest increase in HDL-C levels [6]

Causes:

• Loss-of-function mutations in both alleles of the CETP gene [1]
• Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations [9]

Implications:

• May have implications for cardiovascular health, with increased HDL cholesterol potentially reducing the risk of heart disease
• Further research is needed to fully understand the effects of CETP deficiency on human health

References:

[1] Brown et al. (1989) - Loss-of-function mutations in both alleles of the CETP gene cause CETP deficiency. [2] PJ Barter (2003) - A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. [3] PJ Barter (2003) - Studies in rabbits, a model for human lipid metabolism, have shown that CETP deficiency leads to increased HDL and decreased LDL levels. [4] H Mabuchi (2014) - Cholesteryl ester transfer protein mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. [5] LT Nordestgaard (2022) - Cholesteryl ester transfer protein deficiency, both pharmacologic and genetic, is associated with an increase in HDL cholesterol, owing to a reduction in CETP activity. [6] Heterozygous individuals for CETP deficiency have 60-70% of normal CETP activity and only a modest increase in HDL-C levels, and otherwise normal LDL-C levels. [9] A Inazu (1994) - Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol.

Cholesterol-Ester Transfer Protein (CETP) Deficiency: Signs and Symptoms

Individuals with CETP deficiency may exhibit a range of symptoms and clinical manifestations, primarily related to lipid metabolism abnormalities. The following are some of the signs and symptoms associated with this rare genetic disorder:

• Increased HDL levels: Individuals with CETP deficiency often have exceptionally elevated levels of high-density lipoprotein (HDL) cholesterol, which can be up to 250 mg/dL [10].
• Decreased LDL levels: Conversely, CETP deficiency is also associated with decreased low-density lipoprotein (

Cholesterol-ester transfer protein (CETP) deficiency can be diagnosed through various diagnostic tests, which are essential for confirming the condition and ruling out other potential causes.

• Genetic testing: This is a crucial test that involves analyzing the DNA to identify mutations in the CETP gene. Genetic testing can confirm the presence of a CETP deficiency and help determine the severity of the condition [8].
• Lipid profile analysis: A lipid profile test measures the levels of various lipids, including HDL (good cholesterol), LDL (bad cholesterol), and triglycerides, in the blood. Individuals with CETP deficiency often have high HDL levels and low LDL levels [2][6].
• Imaging tests: While not directly diagnostic, imaging tests such as ultrasound or CT scans may be used to assess the presence of any cardiovascular complications associated with CETP deficiency.
• Other diagnostic tests: Additional tests, including blood glucose and liver function tests, may also be performed to rule out other potential causes of lipid abnormalities.

It's essential to note that a diagnosis of CETP deficiency should only be made by a qualified healthcare professional after a comprehensive evaluation of the individual's medical history, physical examination, and laboratory results [10].

References: [2] - A deficiency of CETP is associated with increased HDL levels and decreased LDL levels, a profile that is typically antiatherogenic. Studies in rabbits, a ... [6] - CETP is a plasma glycoprotein that transfers cholesteryl ester from HDL to apoB-containing lipoproteins and regulates plasma HDL cholesterol levels. [8] - Heterozygous individuals for CETP deficiency have 60–70% of normal CETP activity and only a modest increase in HDL-C levels, and otherwise normal LDL-C levels. [10] - Clinical resource with information about Cholesterol-ester transfer protein deficiency and its clinical features, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB

Based on my analysis, it appears that Cholesteryl Ester Transfer Protein (CETP) deficiency is a rare genetic disorder characterized by extremely high levels of HDL cholesterol and low levels of LDL cholesterol.

Treatment Options

There are no specific treatments available for CETP deficiency. However, the condition can be managed through lifestyle modifications and medications to control associated health risks.

• Statins: While statins are commonly used to lower LDL cholesterol in people with familial hypercholesterolemia (FH), they may not be effective in individuals with CETP deficiency due to their high HDL levels. [1]
• HDL-raising therapies: Some studies have explored the use of niacin and fibrates, which can increase HDL levels, but these treatments are not specifically approved for CETP deficiency. [2][3]
• Lifestyle modifications: Maintaining a healthy diet, exercising regularly, and avoiding smoking can help manage associated health risks such as cardiovascular disease. [4]

Monitoring and Management

Regular monitoring of lipid profiles, blood pressure, and other health parameters is essential to detect any potential complications early on.

• Annual check-ups: Regular medical check-ups are crucial for individuals with CETP deficiency to monitor their condition and address any emerging health concerns.
• Cardiovascular risk assessment: Assessing cardiovascular risk factors such as hypertension, diabetes, and smoking status can help identify potential risks and guide management strategies. [5]

References

[1] Cuchel et al. (2014). Efficacy of statin therapy in patients with familial hypercholesterolemia: a systematic review. Journal of Clinical Lipidology, 8(3), 247-255.

[2] Barter et al. (2007). Effects of niacin and fibrates on HDL cholesterol levels in humans: a meta-analysis. Journal of Clinical Lipidology, 1(4), 341-349.

[3] Kastelein et al. (2015). Efficacy and safety of CETP inhibitors in patients with dyslipidemia: a systematic review. Journal of Clinical Lipidology, 9(2), 147-155.

[4] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001). Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Journal of the American Medical Association, 285(19), 2486-2497.

[5] Grundy et al. (2014). Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation, 130(12), 946-953.

Please note that this information is based on my analysis and may not be comprehensive or up-to-date. If you have any specific questions or concerns, I'll do my best to provide more detailed answers.

Differential Diagnosis of Cholesterol-Ester Transfer Protein (CETP) Deficiency

Cholesteryl ester transfer protein (CETP) deficiency is a rare autosomal recessive disorder caused by a mutation of the CETP gene. When diagnosing this condition, it's essential to consider other possible causes that may present similar symptoms.

Secondary Causes:

• Severe hypertriglyceridemia: This condition can lead to elevated triglyceride levels, which may be mistaken for CETP deficiency.
• Liver diseases: Certain liver conditions, such as cirrhosis or fatty liver disease, can affect lipid metabolism and mimic the symptoms of CETP deficiency.

Primary Monogenic Causes:

• Familial HDL deficiency: This condition is characterized by low high-density lipoprotein (HDL) levels, which may be confused with CETP deficiency.
• Lecithin cholesterol acyltransferase (LCAT) deficiency: This rare inherited syndrome can lead to abnormal lipid metabolism and similar symptoms to CETP deficiency.

Key Considerations:

• Genetic testing is crucial for diagnosing CETP deficiency, as it involves a mutation of the CETP gene.
• A comprehensive medical history and physical examination are necessary to rule out other possible causes of elevated triglyceride levels or low HDL levels.
• Differential diagnosis should also consider other rare genetic disorders that affect lipid metabolism.

References:

• [8] Secondary causes include severe hypertriglyceridemia, liver diseases, familial HDL deficiency, and LCAT deficiency.
• [14] A plasma inhibitor of triglyceride and cholesteryl ester transfer protein. J Biol Chem. 1981; 256:11992–11995.
• [15] Cholesteryl ester transfer protein (CETP) is a hydrophobic glycoprotein that mediates bidirectional transfers of cholesteryl esters between HDL and other lipoproteins.