[Inborn errors of high-density lipoprotein metabolism]

Area of Science:

• Cardiovascular Medicine
• Human Genetics
• Biochemistry

Background:

• Abnormal high-density lipoprotein cholesterol (HDL-C) levels, both low and very high, are linked to increased atherosclerotic cardiovascular disease (ASCVD) risk and reduced life expectancy.
• Common causes include underlying diseases, lifestyle factors, or medications, necessitating their exclusion.
• Less frequently, monogenic disorders affecting genes like APOA1, ABCA1, LCAT, CETP, LIPC, and SCARB1 result in extreme HDL-C levels.

Purpose of the Study:

• To highlight the significance of genetic and biochemical diagnostics in identifying monogenic causes of dysregulated HDL-C.
• To outline clinical and laboratory indicators suggestive of monogenic HDL disorders.
• To emphasize the importance of managing cardiovascular and renal complications in affected individuals.

Main Methods:

• Review of literature on HDL-C metabolism, genetics, and associated diseases.
• Analysis of clinical presentations and diagnostic approaches for monogenic HDL disorders.
• Discussion of current management strategies for cardiovascular and renal complications.

Main Results:

• Monogenic defects in specific genes (APOA1, ABCA1, LCAT, CETP, LIPC, SCARB1) can lead to very low or very high HDL-C levels.
• Clinical manifestations such as corneal opacities, xanthomas, hepatomegaly, and neuropathy can be indicative of these genetic conditions.
• Genetic sequencing and biochemical analysis are crucial for definitive diagnosis, particularly in cases of absolute HDL deficiency or early-onset ASCVD.

Conclusions:

• Monogenic HDL diseases, while rare, necessitate specific diagnostic considerations.
• Early identification through genetic and biochemical testing is vital for individuals with suggestive clinical or laboratory findings.
• Management focuses on preventing cardiovascular and renal complications through cholesterol and blood pressure control, as no specific treatment exists for the genetic defects themselves.