Lipid Metabolic Disorders Flashcards
Familial hypercholesterolaemia is type ____.
Type IIa.
Type IIa is _____________.
Familial hypercholesterolaemia.
In type IIa, ________ and ________ are approximately twice the average.
IIa: total cholesterol and LDL cholesterol are twice the normal average.
Heterozygous IIa affects around 1 in ______ of the population.
1 in 500 people are IIa heterozygotes.
Tendon xanthoma is associated with type _______.
Bonus: non-specific signs are premature (<45yo) corneal arcus.
Type IIa - familial hypercholesterolaemia.
Bonus: also premature (<45yo) corneal arcus (but not specific to FH).
A defect or deficiency in LDLr is the defining trait of _______ hyperlipidaemia.
Type IIa.
What is the pathophysiological basis of type IIa hyperlipidaemia?
LDLr deficiencies slash defects. Or ApoB- defects. For some reason or another there’s just not enough LDLr-ligand binding.
What is the metabolic consequence of inadequate LDLr binding?
Highly elevated LDL cholesterol.
Likewise elevated total cholesterol.
The inheritance pattern for type IIa (FH) is _________________.
Autosomal codominant.
Why does diagnostic testing require fasting samples?
To eliminate the confounding presence of postprandial triglycerides in CMs and VLDLs.
The molecular basis for Tangiers Disease is?
Defective ABCA1 transporter (9q31).
What is the consequence of ABCA1 deficiency?
Complete HDL absence in homozygotes;
About 1/2 [HDL] in heterozygotes.
What is the inheritance pattern of FH and Tangiers disease?
Autosomal codominant.
What are the clinical manifestations of Tangier Disease?
Hepatosplenomegaly
Premature coronary disease
Neuropathy (penetrance 50%)
What are the pathological consequences of ABCA1 defectiveness?
Impaired cholestrol efflux from macrophages,
Impair intracellular lipid trafficking,
Increase presence of foam cells in macrophages and other RES cells throughout the body.
What is the most debilitating aspect of Tangiers disease?
The neuropathy.
What are some clinical features of Tangier Disease among HOMOZYGOTES?
cholesterol ester deposition on -
tonsils (orange tonsils)
liver, spleen, GIT, lymph nodes, bone marrow and Schwann cells.
What is the mainstay treatment of Tangier Disease? What is the likely benefit?
LOW FAT DIET.
Expected symptomatic improvement to peripheral neuropathy.
What therapeutic angles are being explored for Tangier Disease?
Increasing ABCA1 expression
Preventing HDL cholesterol catabolism
Increasing hepatic uptake of HDL cholesterol.
1 in 1million is the prevalence of _________.
Familial chylomicronaemia syndrome.
Type I on the Frederickson classification is….
…. familial chylomicronaemia syndrome (FCS).
FCS is what type on the Frederickson classification?
Type I.
The inheritance pattern of FCS is ___________
autosomal recessive.
Mutations in ______ and also in _______ are the basis of FCS.
Lipoprotein lipase as well as ApoC-II.
