Hemochromatosis

Question 1

Hereditary hemochromatosis

Answer 1

Disease of iron overload –> results in excess iron absorption in the small intestine

Iron travels through the body & accumulates in a wide variety of organs –> oxidation –> generation of free radicals –> damages organs

Question 2

Hereditary hemochromatosis

Genetics

Answer 2

AR

Mutated gene: HFE
Location: 6p21.3

Question 3

HFE protein

Answer 3

Cell-surface protein that i/a w/ transferrin receptor (TfRI) & regulated hepcidin gene expression

Question 4

Hereditary hemochromatosis

Sx & Age of onset

Answer 4

Late onset

All sx relate to iron overload in the tissues: fatigue, joint pain, liver enlargement, cirrhosis, diabetes, increased skin pigment, decreased libido, hypogonadism, arthropathy, cardiomyopathy, hepatocellular carcinoma (30% pts w/ cirrhosis)

Question 5

HFE Mutation

Inheritance

Answer 5

One of most common disorders in N. European pop

Heterozygous: 1 in 8
Homozygous: 1/200-1/400

Question 6

Transferrin

Answer 6

Transports iron in the blood/circulation

Question 7

Iron comes from …

Answer 7

Diet or cellular breakdown (esp RBC via macrophages)

Question 8

Ferrous Iron

Answer 8

Fe+2
Iron w/in hgb

Question 9

Ferric Iron

Answer 9

Fe+3
Iron that is transported & stored

Better to store as Fe2+ can produce free radical – spont oxidation

Question 10

Hepcidin Protein

Answer 10

Represses iron transport in gut

Inhibits iron release from macrophages & other cells

Hormone produced by the liver (released into blood)

Neg control: High iron: Hepcidin increases
Low iron: Hepcidin decreases

Question 11

Ferroportin