Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a genetic condition in which mutations in the LDL receptor (or related proteins — APOB, PCSK9) prevent the liver from clearing LDL from circulation. The result: LDL cholesterol is high from birth (typically >190 mg/dL in untreated heterozygous adults, often >250 mg/dL). Untreated, men face a 50% risk of myocardial infarction by age 50 and women by age 60. Heterozygous FH affects roughly 1 in 250 people globally — making it one of the most common genetic diseases — yet the majority remain undiagnosed. The diagnosis is clinical (Dutch Lipid Clinic Network score) plus genetic confirmation where available; treatment is statin + ezetimibe + PCSK9 inhibitor stacked to drive LDL down aggressively.

• LDL cholesterol — the defining variable; >190 mg/dL untreated in adults is suspicious, especially with family history.
• Total cholesterol — typically >310 mg/dL untreated.
• Apolipoprotein B (ApoB) — directly measures atherogenic particle number; useful adjunct.
• Lipoprotein(a) — independent genetic CV risk; co-inherits in some FH families.
• HDL — usually normal in FH.
• Triglycerides — usually normal; high triglycerides suggest a different lipid disorder.

FH is silent until the first cardiovascular event. Physical signs in advanced cases:

• Tendon xanthomata — cholesterol deposits over Achilles and finger extensor tendons
• Xanthelasma — yellowish cholesterol plaques on eyelids
• Corneal arcus before age 45
• Premature coronary artery disease in the patient or first-degree relatives