Fundamentals Block 3: Familial Hypercholesterolemia and Cystic Fibrosis

What is the inheritance pattern of Familial Hypercholesterolemia and what is the incidence rate?

Familial Hypercholesterolemia is a form of Type II hyperlipoproteinemia
→ it is an autosomal dominant disease
→ Heterozygous 1:500
→ Homozygous is rare and is 1:1,000,000

What is the fundamental basis of why Familial Hypercholesterolemia causes increased serum cholesterol?

Familial Hypercholesterolemia causes defective LDL-C receptors which will trigger increased levels of LDL within the blood
→ this leads to a buildup of cholesterol within your arteries resulting in increased serum cholesterol

What is the clinical manifestations of Familial Hypercholesterolemia?

There are four main manifestations
1) Premature atherosclerosis (plaque formation on the arterial wall) leading to early myocardial infarction (heart attack)

2) Arcus lipoides corneae or deposits of lipids on the outer region of the cornea

3) Tuberous/tendon xanthomas (especially the Achilles tendon) in type IIa - basically firm nodules made of lipoproteins in the tendons

4) Xanthelasma - lipid filled deposits in the eyelids

What is the inheritance pattern of Cystic Fibrosis and what is the incidence rate?

An autosomal recessive disorder commonly found in Europeans
→ incidence rate 1:3500

How would the transepithelial potential in the sweat duct differ in a CF patient compared to a normal person?

Would it be hyperpolarized, depolarized or would it be the same as a normal sweat duct?

the transepithelial potential will be considerably more negative than in a normal person as the chloride channel fails and salt reabsorption fails
→ hyperpolarized

Why do Cystic Fibrosis patients have a high salt concentration in their sweat?

The defective ATP-gated chloride channels in the sweat glands causes an inability to reabsorb Chloride Ions from the lumen of the sweat glands

→ this impairs the ability to reabsorb Sodium and Water leading to elevated sodium concentrations in sweat

What causes Cystic Fibrosis?

mutation of the CFTR gene which causes a mutation that results in defective chloride channels