Differential diagnosis of familial high density lipoprotein deficiency syndromes

Area of Science:

• Biochemistry
• Genetics
• Cardiovascular Medicine

Background:

• Monogenic high density lipoprotein (HDL) deficiency is characterized by HDL cholesterol levels below the fifth percentile.
• Defects in apolipoprotein A-I (apoA-I), adenosine triphosphate binding cassette transporter A1 (ABCA1), or lecithin:cholesterol acyltransferase (LCAT) genes cause this condition.

Purpose of the Study:

• To outline the diagnostic approach for monogenic HDL deficiency.
• To emphasize the importance of excluding underlying diseases and identifying clinical hallmarks.

Main Methods:

• Exclusion of secondary causes of low HDL cholesterol.
• Physical examination for clinical signs of HDL deficiency syndromes.
• Family studies to assess vertical transmission of the phenotype.
• Specialized biochemical tests and genetic analysis of apoA-I, ABCA1, and LCAT genes.

Main Results:

• Diagnosis requires identifying a functionally relevant mutation in one of the key genes.
• Low HDL cholesterol phenotype often shows vertical transmission within families.

Conclusions:

• No current drugs effectively raise HDL cholesterol in familial low HDL cholesterol patients.
• Cardiovascular disease prevention strategies should focus on managing other risk factors.