Lipid Metabolic Disorders

Question 1

Familial hypercholesterolaemia is type ____.

Answer 1

Type IIa.

Question 2

Type IIa is _____________.

Answer 2

Familial hypercholesterolaemia.

Question 3

In type IIa, ________ and ________ are approximately twice the average.

Answer 3

IIa: total cholesterol and LDL cholesterol are twice the normal average.

Question 4

Heterozygous IIa affects around 1 in ______ of the population.

Answer 4

1 in 500 people are IIa heterozygotes.

Question 5

Tendon xanthoma is associated with type _______.

Bonus: non-specific signs are premature (<45yo) corneal arcus.

Answer 5

Type IIa - familial hypercholesterolaemia.

Bonus: also premature (<45yo) corneal arcus (but not specific to FH).

Question 6

A defect or deficiency in LDLr is the defining trait of _______ hyperlipidaemia.

Answer 6

Type IIa.

Question 7

What is the pathophysiological basis of type IIa hyperlipidaemia?

Answer 7

LDLr deficiencies slash defects. Or ApoB- defects. For some reason or another there’s just not enough LDLr-ligand binding.

Question 8

What is the metabolic consequence of inadequate LDLr binding?

Answer 8

Highly elevated LDL cholesterol.

Likewise elevated total cholesterol.

Question 9

The inheritance pattern for type IIa (FH) is _________________.

Answer 9

Autosomal codominant.

Question 10

Why does diagnostic testing require fasting samples?

Answer 10

To eliminate the confounding presence of postprandial triglycerides in CMs and VLDLs.

Question 11

The molecular basis for Tangiers Disease is?

Answer 11

Defective ABCA1 transporter (9q31).

Question 12

What is the consequence of ABCA1 deficiency?

Answer 12

Complete HDL absence in homozygotes;

About 1/2 [HDL] in heterozygotes.

Question 13

What is the inheritance pattern of FH and Tangiers disease?

Answer 13

Autosomal codominant.

Question 14

What are the clinical manifestations of Tangier Disease?

Answer 14

Hepatosplenomegaly
Premature coronary disease
Neuropathy (penetrance 50%)

Question 15

What are the pathological consequences of ABCA1 defectiveness?

Answer 15

Impaired cholestrol efflux from macrophages,
Impair intracellular lipid trafficking,
Increase presence of foam cells in macrophages and other RES cells throughout the body.

Question 16

What is the most debilitating aspect of Tangiers disease?

Answer 16

The neuropathy.

Question 17

What are some clinical features of Tangier Disease among HOMOZYGOTES?

Answer 17

cholesterol ester deposition on -
tonsils (orange tonsils)
liver, spleen, GIT, lymph nodes, bone marrow and Schwann cells.

Question 18

What is the mainstay treatment of Tangier Disease? What is the likely benefit?

Answer 18

LOW FAT DIET.

Expected symptomatic improvement to peripheral neuropathy.

Question 19

What therapeutic angles are being explored for Tangier Disease?

Answer 19

Increasing ABCA1 expression
Preventing HDL cholesterol catabolism
Increasing hepatic uptake of HDL cholesterol.

Question 20

1 in 1million is the prevalence of _________.

Answer 20

Familial chylomicronaemia syndrome.

Question 21

Type I on the Frederickson classification is….

Answer 21

…. familial chylomicronaemia syndrome (FCS).

Question 22

FCS is what type on the Frederickson classification?

Answer 22

Type I.

Question 23

The inheritance pattern of FCS is ___________

Answer 23

autosomal recessive.

Question 24

Mutations in ______ and also in _______ are the basis of FCS.

Answer 24

Lipoprotein lipase as well as ApoC-II.

Question 25

ApoC-II mutations are a feature of:

• FHS
• FH or
• TD?

Answer 25

FHS (type I hyperlipidaemia).

Question 26

LPL mutations are a feature of:

• FHS
• FH or
• TD?

Answer 26

FHS (type I hyperlipidaemia).

Question 27

What are the clinical manifestations of familial chylomicronaemia syndrome?

Answer 27

1. ERUPTIVE xanthomas
2. hepatosplenomegaly
3. pancreatisis

Question 28

About 1 in ______ of the population have FH with mutations in the LDLR gene. FH with mutations in the ______ gene have less than half that frequency.

Answer 28

1:500 LDLR mutations

<1:1000 APOB mutations.

Question 29

About 1 in ______ of the population have FCS with mutations in the LPL gene. FH with mutations in the ______ gene are put as less than that.

Answer 29

1:1million FCS have LPL mutations.

<1:1million FCS have APOC mutations.

Question 30

In familial hypercholesterolaemia, ________ are normal and ___ are typically either _______ or slightly __________.
Of course, LDLs are __________.

Answer 30

Triglycerides: normal
HDL: normal or slightly lowered N/-
LDL: elevated +++

Question 31

Pacreatisis is a big problem indicative of ____________.

Answer 31

Familial chylomicronaemia syndrome.

Question 32

In FHS, HDLs are ______, LDLs are ________ but total cholesterol is ________.

Answer 32

HDL: very low (—)
LDL: low (-)
Total cholesterol: slightly elevated (+)

Question 33

Plasma in type I appears ________ and in type IIa it appears _________.

Answer 33

FHS: lactescent
FH: clear

Question 34

You need to check the lecture for the lysosomal storage disorders slide.

Answer 34

You need to check the lecture for the lysosomal storage disorders slide.