Diagnosis and treatment of high density lipoprotein deficiency

Area of Science:

• Cardiovascular Medicine
• Human Genetics
• Biochemistry

Background:

• Low serum high-density lipoprotein cholesterol (HDL-C) is an independent risk factor for cardiovascular disease (CVD).
• Marked deficiency of HDL-C (<20 mg/dL) without secondary causes affects less than 1% of the population.
• This deficiency is often associated with hypertriglyceridemia, obesity, insulin resistance, and diabetes.

Purpose of the Study:

• To describe the genetic basis and clinical presentation of patients with severe HDL-C deficiency.
• To highlight the diagnostic necessity of DNA analysis in these rare cases.
• To emphasize the importance of managing non-HDL risk factors.

Main Methods:

• Review of genetic defects associated with severe HDL-C deficiency.
• Analysis of clinical presentations and associated conditions.
• Discussion of diagnostic approaches, including DNA analysis.

Main Results:

• Severe HDL-C deficiency can result from homozygous, compound heterozygous, or heterozygous defects in APOAI, ABCA1, or lecithin:cholesterol acyl transferase genes.
• Associated genetic conditions include apo A-I deficiency, apoA-I variants, Tangier disease, familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease.
• Clinical manifestations include premature CVD, neuropathy, kidney failure, hepatosplenomegaly, and anemia.

Conclusions:

• Severe HDL-C deficiency is a rare genetic disorder with significant health implications, including premature cardiovascular disease.
• Diagnosis requires genetic analysis due to variability in presentation.
• Optimal management involves addressing all non-HDL risk factors.