Marked decrease in plasma apolipoprotein A-I and high density lipoprotein-cholesterol in a case with Werner syndrome

Area of Science:

• Biochemistry
• Genetics
• Clinical Medicine

Background:

• Werner syndrome is a rare premature aging disorder.
• Lipid metabolism disorders, including low high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I), are common in Werner syndrome.
• The genetic basis for these lipid abnormalities is not fully understood.

Observation:

• A 39-year-old male with Werner syndrome exhibited significant decreases in plasma HDL-C and apo A-I levels.
• These decreases were accompanied by a reciprocal increase in plasma triglyceride (TG) levels.
• Lipoprotein lipase (LPL) activity and mass were markedly reduced during the period of low HDL-C and apo A-I.

Findings:

• No mutations were found in the apolipoprotein A-I (apo A-I) gene, suggesting the lipid changes are not due to direct genetic defects in apo A-I.
• Impaired hydrolysis of triglycerides in triglyceride-rich lipoproteins was observed.
• Reduced formation of nascent HDL particles was inferred from the low apo A-I and HDL-C levels.

Implications:

• Decreased lipoprotein lipase (LPL) levels contribute to impaired TG hydrolysis and reduced HDL formation in this Werner syndrome patient.
• These findings highlight a potential mechanism for dyslipidemia in Werner syndrome, independent of direct apo A-I gene mutations.
• Understanding these mechanisms could inform future therapeutic strategies for managing lipid disorders in Werner syndrome.