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