Unit 4 Small Group Session

Question 1

What are the 2 forms of systemic carnitine deficiency?

Answer 1

1. Deficiency of carnitine transporter

2. Deficiency of CPT

Question 2

What is the primary form of carnitine deficiency?

Answer 2

Deficiency of the transporter

Question 3

How can you tell someone doesn’t have the transporter deficiency?

Answer 3

If liver and other tissues are also affected, then it’s unlikely to be a deficiency of the transporter as the liver has one transporter type and other tissues have another transporter type

Question 4

How does primary carnitine deficiency impact plasma and tissue carnitine levels

Answer 4

Decreases both (kidneys can’t reabsorb carnitine into plasma due to transporter defect)

Question 5

How do you treat primary carnitine deficiency?

Answer 5

Diet high in carnitine - high levels “push” the transporter

Question 6

What is secondary carnitine deficiency?

Answer 6

A deficiency in either CPT II (mostly) or in CPT1 (rare and lethal)

Question 7

What is the impact of secondary carnitine deficiency on fatty acids

Answer 7

Causes defective beta oxidation of fatty acids

Question 8

How is the carnitine pool depleted in secondary carnitine deficiency

Answer 8

Acyl-carnitines accumulate and are excreted in the urine

Question 9

What is the impact of acyl carnitines on free carnitine uptake?

Answer 9

Inhibitory

Question 10

What are some symptoms associated with secondary carnitine deficiency (CPTII, severe form)

Answer 10

hypoketotic hypoglycemia, hyperammonemia, cardiac malfunction, and sometimes death

Question 11

What are some symptoms associated with secondary carnitine deficiency (CPT II, mild form)

Answer 11

Muscle weakness during prolonged exercise, myoglobinuia (due to breakdown of muscle tissue)

Question 12

How can you precipitate symptoms of the severe form of CPT II deficiency?

Answer 12

Periods of fasting

Question 13

How do you treat secondary carnitine deficiency

Answer 13

Low fat diet, high carbohydrate diet, avoid fasting, supplement with medium chain FAs

Question 14

Why is there general weakness and muscle tone in carnitine deficiency?

Answer 14

Due to insufficient substrates for energy metabolism

Question 15

Why is there fasting hypoglycemia in carnitine deficiency?

Answer 15

impaired long chain FA metabolism means you can’t use FA for energy and need to use the glucose

Question 16

What happens to glycogen stores during fasting in carnitine deficiency?

Answer 16

Depleted quickly

Question 17

Why can’t people who have carnitine deficiency do effective gluconeogenesis during a fast?

Answer 17

Gluconeogenesis requires ATP, most of which comes from B-oxidation of FA, which can’t be performed without carnitine

Question 18

Tissues that would use FA end up using _______

Answer 18

glucose

Question 19

Why is there elevated FA in blood in carnitine deficiency?

Answer 19

decreased glucose levels lead to increased epinephrine, and epinephrine mobilizes TAGs of adipose tissue which

Question 20

Why is there an absence of ketoacids following fasting in carnitine deficiency?

Answer 20

ketone synthesis requires acetyl CoA

Question 21

Why is there an accumulation of tissue and plasma TAGs in carnitine deficiency?

Answer 21

Fatty acid excess is diverted and fed into other pathways like TAG synthesis

Question 22

Why is there hyperammonemia in carnitine deficiency?

Answer 22

Ureagenesis requires ATP, which comes primarily from B-oxidation

Question 23

What are the two defects that can cause HLD Type IIA

Answer 23

1. LDL receptor defect

2. Defect in the ligand-binding region of Apo-B-100

Question 24

Statins inhibit what enzyme?

Answer 24

HMG-CoA Reductase

Question 25

Why does HLD Type IIA cause tendinous and cutaneous xanthomas?

Answer 25

Excess cholesterol deposits in tendons, skin, and cornea

Question 26

Why is there elevated serum cholesterol in homozygotes of HLD Type IIA

Answer 26

Cholesterol cannot be removed from circulation to be delivered to tissues

Question 27

How do statins increase LDL receptor synthesis?

Answer 27

Inhibit endogenous synthesis of cholesterol by inhibiting HMG-CoA Reductase, increase LDL receptor synthesis

Question 28

Why are statins ineffective against homozygotes with HLD Type IIA

Answer 28

Because they have two bad copies of receptors, so you’d just be upregulating bad receptors

Question 29

What is the LDL concentration, relative to normal, in people with familial hypercholesterolemia

Answer 29

elevated

Question 30

What is the inheritance pattern of familial hypercholesterolemia

Answer 30

Autosomal dominant

Question 31

What is the primary defect in familial hypercholesterolemia

Answer 31

LDL receptor mutation

Question 32

What is the function of normal LDL receptors

Answer 32

Bind LDL and facilitate its uptake by endocytosis. LDL gets degraded in lysosome, and the cholesterol is released for use

Question 33

What happens due to the defective LDL receptor in familial hypercholesterolemia

Answer 33

Decreased rate of LDL removal from plasma

Question 34

At what rate do heterozygotes bind and take up LDL in familial hypercholesterolemia

Answer 34

50% of normal rate