Case 5

Question 1

What type of disorder is heterozygous hypercholesterolemia?

Answer 1

autosomal codominant

Question 2

What is the average level of cholesterol in heterozygous hypercholesterolemia patients?

Answer 2

300 to 600mg

Question 3

what symptoms are associated with hypercholesterolemia (FH)?

Answer 3

• tendinous and tuberous xanthomas in skin

- Arcus in cornea

Question 4

cholesterol elevation is associated with what?

Answer 4

increase in LDL-C

- can synthesize intracellular cholesterol but lack in their receptors

Question 5

What are the classes of defects in LDL receptors in FH?

Answer 5

• Class 1: no LDL receptor
• Class 2: membrane protein not transported to golgi and degraded
• Class 3: LDL receptor can’t bind to LDL
• Class 4: LDL receptor cannot internalize LDL and transport it to golgi
• Class 5: LDL receptors don’t recycle

Question 6

Which type of mutation is the most common?

Answer 6

Class 2 mutation

Question 7

How do cells obtain cholesterol when receptors are lacking?

Answer 7

make intracellular cholesterol to compensate

Question 8

In FH heterozygotes, how do we reduce cholesterol?

Answer 8

by using HMG-CoA reductase inhibitors (statins)

Question 9

How do statins decrease cholesterol levels?

Answer 9

by increasing LDL receptors (in liver mainly) to remove LDL from the circulation

Question 10

How do we treat FH homozygotes?

Answer 10

LDL pheresis 4

Question 11

how high are TAG levels in borderline, high, and very high triglyceridemia?

Answer 11

• borderline: 150-200
• high: 200 - 500
• very high: more than 500

Question 12

what are the causes of hypertriglyceridemia?

Answer 12

• familial hypertriglyceridemia

- secondary to hormonal abnormalities, diabetes, or nephrosis

Question 13

how does diabetes cause hypertriglyceridemia?

Answer 13

shunting of glucose pathway into pentose pathway, leading to increased fatty acid synthesis

Question 14

how does renal failure cause hypertriglyceridemia?

Answer 14

depresses removal of large-molecular-weight constituents like TAG

Question 15

What hormones can affect TAG levels and how?

Answer 15

• epinephrine & norepinephrine, growth hormone, ACTH, thyrotropin, and glucagon
• by triggering production of hormone sensitive lipase located on adipose tissue