16 - Rare Lipid Disorders

Question 1

What lipids do we measure

Answer 1

• Total cholesterol
• HDL cholesterol
• Triglycerides
• LDL cholesterol (calculated)

Question 2

Apolipoprotein (apo) B

Answer 2

• Essential for the formation of triglyceride-rich lipoproteins
• Liver secretes full length apoB
• Intestine secretes 48% of length
• Both forms are encoded by the APOB gene on chromosome 2

Question 3

Inherited lipid disorders

Answer 3

• Familial hypercholesterolaemia (high LDL –> increased cvd risk)
• Familial dysbetalipoproteinemia (high HDL –> increased CVD risk)
• Familial chylomicronemia syndrome (high TG –> increased pancreatitis risk)
• Anderson disease (low LDL)
• Tangier disease (low HDL)

Question 4

Genetic causes of hypoalphalipoproteinaemia

Answer 4

• Tangier disease
• ApoA-I deficiency
• LCAT deficiency

Question 5

Lipoprotein lipase (LPL) deficiency

Answer 5

• Rare autosomal recessive disorder characterised by high triglycerides and absence of LPL activity
• Clinical manifestations (usually from early childhood) include abdominal pain, episodes of pancreatitis, xanthoma
• Treatment: strict adherence to a low fat diet

Question 6

Alipogene tiparvovec (glycera, million dollar drug)

Answer 6

• Adeno associated virus based gene therapy
• Increased LPL activity, reduces plasma triglycerides and lowers risk of pancreatitis

Question 7

Hypobetalipoproteinemia

Answer 7

• Low LDL and apoB
• Vegan, malnutrition, hyperthyroidism
• Mainly familial

Question 8

APOB mutations

Answer 8

• Cause low cholesterol
• Most mutations result in production of truncated apoB

Question 9

Mipomersen

Answer 9

• An ApoB Antisense Oligonucleotide that Lowers Cholesterol
• Treatment of homozygous familial hypercholesterolaemia

Question 10

Abetalipoproteinaemia

Answer 10

• Very rare autosomal recessive disorder of lipid metabolism
• Absence of apoB containing lipoproteins
• Fatty liver and intestine
• Mutations in the MTTP gene

Question 11

Lomitapide

Answer 11

• Targets MTTP
• Small molecule inhibitor
• Reduces intestinal and liver apoB containing lipoprotein production

Question 12

PCSK9 inhibitors

Answer 12

• Monoclonal antibodies
• Reduces LDL-cholesterol by ~60% in
  hypercholesterolaemia patients already taking statins
• Expensive