General Considerations

Hemochromatosis refers to a group of genetic diseases that predispose to iron overload, potentially leading to fibrosis and organ failure

-Increased accumulation of iron as hemosiderin in the liver, pancreas, heart, testes,adreanls, pituitary, and kidneys

-Major clinical manifestations: Cirrhosis of the liver, diabetes mellitus, arthritis, cardiomyopathy, and hypogonadotropic hypogonadism

-The quantity of total iron is 3 g in women and 5 g in men. Most iron resides in red blood cells.

-Almost all iron absorption occurs in the duodenum.

-Hepcidin normally functions as a regulatory protein which controls iron absorption

-In hemochromatosis, mucosal absorption is greater than body requirements and amounts to ≥4 mg/d.

-Most common autosomal recessive disease in Caucasians

HFE gene mutation (usually C282Y/C282Y) is found in most cases

-C282Y is the major mutation and H63D the minor mutation of the HFE gene

-The onset is usually after age 50

-The disease is more common in men than in women

Symptoms & Signs

-Most patients are aymptomatic

-Lethargy, arthralgia, skin pigmentation, loss of libido, loss of body hair, jaundice, hepatomegaly, cirrhosis, diabetes mellitus, increased pigmentation, spider angiomas, splenomegaly, arthropathy, ascites, cardiac arrhythmias, congestive heart failure, testicular atrophy


-Measure serum iron, tranferrin saturation, ferritin concentration, liver biopsy, MRI liver

-Hepatic iron index generally > 1.9

-An elevated plasma iron with > 45% transferrin saturation

-An elevated serum ferritin

-A TSAT ≥45 percent and/or a serum ferritin >200 ng/mL (>200 mcg/L) in men or >150 ng/mL (>150 mcg/L) in women is consistent with iron overload

-Test for HFE mutations when serum iron/total iron-binding capacity and/or serum ferritin are elevated

-Genetic testing is not recommended for the general population.



-therapy involves removal of the excess body iron and supportive treatment of damaged organs

Iron removal: therapeutic Phlebotomy (mainstay of treatment), Chelating agents (Deferoxamine, Dererasirox)

-counsel and screen other family members

-Stop alcohol consumption

-Liver transplantation for advanced cirrhosis


-Survival appears normal in those with a serum ferritin <2000 ng/mL at the time of diagnosis.

-The principal cause of death are cardiac failure, portal hypertension, liver cancer


Q.What is the most common autosomal-recessive disorder in Caucasians? HFE-related hemochromatosis

  1. What is the single best screening test for hereditary hemochromatosis? Transferrin saturation
  2. What is the key regulatory hormone that controls iron metabolism? Hepcidin
  3. What is the first organ to be affected by hemochromatosis? Liver
  4. What is the most common cardiac manifestation of hemochromatosis? Congestive heart failure
  5. What are the most common endocrine manifestaions of hemochromatosis? Diabetes mellitus and hypogonadism
  6. What is the classic presentation of arthropathy in hemochromatosis? the second and third metacarpophalangeal and proximal interphalangeal joints of the hands

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