Chem Path - lipoproteins

Question 1

What are the dangers of hypercholesterolaemia?

Answer 1

Atherosclerosis - cholesterol is a basic building block of it

Question 2

Familial hypercholesteraemia (type II) (common variant)

Answer 2

Most common cause - LDLR and apoB gene mutations. Autosomal dominant but is still much worse when homozygous.

Loss of function of LDL receptor or apoB genes. ↓LDLR means less removal of LDL from blood.
apoB codes for the protein on the LDL that binds to the receptor so ↓apoB means less binding to LDLR

Yellow deposits of cholesterol-rich fat may be seen in various places on the body such as around the eyelids (known as xanthelasma), the outer margin of the iris (known as corneal arcus), and in the tendons of the hands, elbows, knees and feet, particularly the Achilles tendon (known as a tendon xanthoma).

Question 3

Familial hypercholesteraemia (type II) (Uncommon variant)

Answer 3

PCSK9 - autosomal dominant

Thought to be an LDLR inhibitor - therefore, ↑PCSK9 results in ↓LDLR and therefore ↑LDL in blood. Anti-PCSK9 mAb -novel form of lowering LDL

LDLRAP1 - autosomal recessive

Mechanism unknown. Recessive disease requires 2 ‘bad genes’. Recessive disease is thought to be worse than heterozygous dominant (LDLR, LDLR) but better than homozygous dominant (LDLR, LDLR*)

Question 4

Polygenic Hypercholesteraemia

Answer 4

google doesn’t believe this disease exists, wikipedia redirects you to Familial. Assume that this disease is the same as Familial but with multiple mutations causing it.

Question 5

Familial hyper alpha-lipoproteinaemia

Answer 5

CETP Deficiency

Again, this disease doesn’t exist. However CETP plays a role in making HDLs so a deficiency means ↓HDL, meaning ↑LDL. Still causes a lipoproteinaemia, unlike Tangier Disease, because the HDL precursors still float around in the blood.

Question 6

Phytosterolaemia

Answer 6

Rare autosomal recessive leading to defects in ABC transporters G5 and G8 (in intestines)

↑Absorption of plant sterols. Plant sterols are usually not absorbed and are preferentially excreted into the bile.

May actually have ↑LDLR but not much use since body can’t really do anything about these plant sterols.

Rx - avoid plant sterols

Question 7

Hypertryglyceridaemias

Answer 7

↑Lipids but not cholesterol. Won’t have the xanthalamatic signs.

familial deficiency of lipoprotein lipase, apoC-II (type I) and apoA-V (type V)

Question 8

Tangier Disease

Answer 8

Familial alpha-lipoprotein deficiency caused by ABCA1 mutations

rare autosomal dominant inherited disorder characterized by a severe reduction in the amount of HDLs

Yellow/Orange cholesterol deposits in the tonsils. Deposits can also be found in the liver and spleen, causing hepatosplenomegaly.

Question 9

Aβ-lipoproteinaemia

Answer 9

MTP def

Question 10

Hypoβ-lipoproteinaemia

Answer 10

Truncated apoB protein

Beta = apoB protein

Question 11

Hypoα-lipoproteinaemia

Answer 11

apoA-I mutations (sometimes)

Alpha = apoA protein

Question 12

What is the relationship between lipids and atherogenesis?

Answer 12

LDL α CHD
HDL 1/α CHD

Lipoprotein is best marker as it takes into account VLDLs too. Serum triglyceride is correlated but not as good as others.

However, severe hypertriglyceridaemia (>10 mmol/l) can precipitate acute pancreatitis