Definition and Pathogenesis:
• Intestinal iron absorption is increased in hemochromatosis.
• There is an autosomal recessive HFE gene mutation that causes an increase in iron-binding protein in the intestine.
• Due to this mutation, hepcidin synthesis from the liver, which regulates iron absorption, is decreased.
• The most important mutation is C282Y. H63D is another less important mutation.
• Iron is stored in all tissues and macrophages, especially in the liver and reticuloendothelial system (RES).
• Iron accumulates in the liver, leading to cell damage and the development of chronic hepatitis and cirrhosis.
• A similar picture may occur as a result of excessive iron overload to the body by oral or parenteral route without increasing iron absorption. This is called secondary hemochromatosis. It is most commonly seen in thalassemia patients due to excessive transfusion.
Clinic:
• The most common initial symptom is extreme fatigue. The first and most frequently involved organ is the liver.
• Cirrhosis, skin pigmentation, glucose intolerance, cardiac arrhythmias, first restrictive and then dilated cardiomyopathy, hypogonadism, arthropathy, alopecia, hepatosplenomegaly and hypothyroidism can be seen.
• Arthritis that develops in these patients especially affects the 2nd and 3rd metacarpophalangeal joints.
• It is also known as bronze diabetes because of pancreas and skin involvement.
• 1/3 of patients with cirrhosis develop HCC (high risk of developing HCC).
• The most common causes of death in these patients are cirrhosis complications and HCC.
Lab:
• Iron indices:
Serum ferritin rises (> 1000 µg/ml more specific), used as a screening test.
Fasting transferrin saturation increases (> 45%), ferritin can be found to be positive in the early stages of the disease, it is used for screening, it is recommended to be combined with ferritin.
It has high serum iron and low iron binding capacity.
• A pattern of increased tissue iron is typical on imaging with MRI.
• Genetic testing (C282Y homozygous or C282Y /H63D combined heterozygous) is the gold standard in diagnosis.
• Liver biopsy is performed in patients with high serum ferritin levels (> 1000 µg/L) and/or liver function test abnormalities (because these patients may have developed severe fibrosis).
Treatment:
• The best method is repetitive phlebotomy.
• Monitoring of serum ferritin levels determines the frequency of phlebotomy.
• Arthropathy and hypogonadism do not return with phlebotomy, and HCC risk does not decrease if cirrhosis has developed.
• Iron-binding chelator agents (deferoxamine and deferasirox) are used in patients who cannot undergo phlebotomy.