Hemochromatosis

Question 1

Etiology of hemochromatosis

Answer 1

1) Decreased synthesis or expression of hepcidin (the principal iron regulatory hormone)
2) autosomal recessive disease, mutation of HFE gene protein (important role in duodenal cells sensing iron stores, leading to increased absorption from the duodenum)

Question 2

Two major HFE gene mutations

Answer 2

1) C282Y - homozygous leads to hemochromatosis

2) H63D - homozygotes do not develop hemochromatosis but increased risk of ALS and non-cardia gastric CA

Question 3

Non-HFE gene mutations that can lead to hemochromatosis

Answer 3

1. Transferrin receptor
2. Ferroportin
3. Hemojuvelin (juvenile onset, severe iron overlaod, cardiac dysfunction, hypogonadic hypogonadism, high mortality)
4. Hepcidin

Question 4

Sites of iron deposition

Answer 4

Liver, pancreas, heart, adrenals, testes, pituitary gland, kidneys

Question 5

Hemochromatosis co-morbidities

Answer 5

1) cirrhosis if EtOH or fatty liver present
2) diabetes mellitus
3) heart failure
4) Erectile dysfunction
5) porphyria cutanea tarda
6) colorectal and breast CA
7) Infections - Vibrio, Listeria, Yersinia

Question 6

Signs / sxs

Answer 6

Early: fatigue arthralgias
Later: arthropathy, hepatomegaly with hepatic dysfunction, grey-bronze skin pigmentation, cardiomegaly +/- HF, DM, erectile dysfunction

Question 7

Lab work-up

Answer 7

1) CMP - mildly elevated AST and alk ph
2) elevated plasma iron and >45% transferrin sat, elevated serum ferritin
3) test HFE mutations if any evidence of iron overload

Question 8

Imaging work-up

Answer 8

MRI - may help quantitate hepatic iron stores and assess degree of hepatic fibrosis

Question 9

When do you obtain a liver bx?

Answer 9

1) homozygotes of C282Y to determine if cirrhosis present

Question 10

When can you defer a liver bx?

Answer 10

If serum ferritin <1000 mcg/L and normal AST, no hepatomegaly since likelihood of cirrhosis will be low

Question 11

Labs with high-specificity for cirrhosis in hemochromatosis:

Answer 11

1) serum ferritin >1000 mcg/L, plus…

2) serum hyaluronic acid >46.5 mcg/L

Question 12

Liver bx findings

Answer 12

1) extensive iron deposition in hepatocytes and bile ducts

2) high hepatic iron index >1.9 (hepatic iron content per g of liver converted to micromoles divided by pt’s age)

Question 13

When to screen

Answer 13

Screen a child if one parent is affected and other parent is a known/potential carrier

Question 14

Treatment for hemochromatosis

Answer 14

1) Weekly phlebotomy, 1-2U of blood until % sat <50% and ferritin in 50-100 range, then q3-4months
2) deferoxamine - chelating agent in pts who cannot tolerate phlebotomies
3) avoidance of high iron foods (red meat, alcohol, vit D, raw shellfish, supplemental iron)
4) PPI to decrease intestinal iron absorption
5) liver transplant in advanced cirrhosis