U01.01.136 Familial dyslipidemias

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Learning Objectives

  • Differentiate the four major types of Familial Dyslipidemias by inheritance and blood levels.
  • Identify the pathognomonic clinical findings (e.g., palmar xanthomas, Achilles tendon xanthomas).
  • Explain the biochemical defects involving LPL, Apo CII, Apo B-100, and Apo E.
  • Recognize which types carry an accelerated risk for atherosclerosis.

1. Type I: Hyperchylomicronemia

An autosomal recessive disorder where the body cannot “cut” the triglycerides out of chylomicrons.

  • Pathogenesis: Deficiency in Lipoprotein Lipase (LPL) or its cofactor, Apo CII.
  • Blood Levels: Massive elevation in Chylomicrons and Triglycerides (TG).
  • Clinical: Recurrent acute pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas.
  • Key Note: Surprisingly, there is no increased risk for atherosclerosis. A “creamy” layer forms in the supernatant of standing plasma.

2. Type II: Hypercholesterolemia

An autosomal dominant disorder leading to dangerously high cholesterol levels.

  • Pathogenesis: Absent or defective LDL receptors, or defective Apo B-100.
  • Blood Levels:
    • IIa: Elevated LDL and Cholesterol.
    • IIb: Elevated LDL, Cholesterol, and VLDL.
  • Clinical: Accelerated atherosclerosis (MI can occur before age 20 in homozygotes), tendon (Achilles) xanthomas, and corneal arcus.

3. Type III: Dysbetalipoproteinemia

An autosomal recessive disorder where the liver cannot “grab” remnants.

  • Pathogenesis: Defective Apo E (Defective in Type thrEE).
  • Blood Levels: Elevated Chylomicron remnants and VLDL (IDL).
  • Clinical: Premature atherosclerosis and palmar xanthomas (yellow creases in the palms).

Activity:

4. Type IV: Hypertriglyceridemia

An autosomal dominant disorder is often linked to metabolic health.

  • Pathogenesis: Hepatic overproduction of VLDL.
  • Blood Levels: Elevated VLDL and TG.
  • Clinical: Extremely high triglycerides (> 1000 mg/dL) can cause acute pancreatitis. This type is strongly related to insulin resistance.

Clinical Notes & Corrections:

  • Pancreatitis vs. Atherosclerosis: Types I and IV primarily present with pancreatitis due to TG levels. Types II and III primarily present with premature cardiovascular disease.
  • Apo B-100: Remember that a defect here (Type II) is critical because it is the ligand for the LDL receptor. If the “key” (B-100) or the “lock” (receptor) is broken, LDL stays in the blood.

Activity: Dyslipidemia Matching Challenge

Memory Hooks:

Type 1: 1 is LPL (A is the 1st letter of Apo CII).

Type 2: 2 has 2 letters: L–D-L.

Type 3: 3 involves Apo E (ThrEE).

Type 4: 4 is VLDL (Roman numeral IV looks like V).

Activity: