Tag Archive for: HFE gene mutations

Hereditary Hemochromatosis (HH) is an autosomal recessive genetic disease characterized by abnormalities in iron regulation, mostly due to mutations in the HFE gene, leading to increased iron absorption due to hepcidin deficiency. The classification of HH is based on the type of mutated gene, which must be distinguished from non-genetic conditions that cause secondary elevations in serum iron levels such as multiple transfusions and increased iron supplementation. Pathophysiological mechanisms of HH include increased absorption of iron in the upper intestine, decreased expression of the iron regulatory hormone hepcidin, altered function of the HFE protein, and tissue damage and fibrogenesis caused by iron overload. The human body is physiologically unable to excrete excess iron load so excess iron in serum will be deposited in various organs, causing organ dysfunction. The clinical manifestations of hemochromatosis vary widely depending on the location of iron deposition in the organ. The classic clinical triad of hemochromatosis is liver cirrhosis, skin pigmentation, and diabetes mellitus. Hemochromatosis can be screened for and diagnosed by examining serum ferritin levels, transferrin saturation, unsaturated iron-binding capacity, total iron-binding capacity, liver biopsy, magnetic resonance imaging, and genetic testing. The main treatment for hemochromatosis at this time is phlebotomy although other therapeutic methods can also be used to help lower iron levels and improve the patient’s clinical course, such as therapy with chelating agents, erythrocytopharesis, and liver transplantation. If hemochromatosis is not treated, the patient can experience progressive liver damage leading to cirrhosis and hepatocellular carcinoma, and complications due to damage to various tissues and organs.