Red Blood Cells Associated Disorder: Hemochromatosis: Assessment, Analysis, and Associated Dental Management Guidelines
Hereditary hemochromatosis (HHC), due to mutations in the HFE gene, is an autosomal recessive disorder of iron metabolism. Human hemochromatosis protein, also known as the HFE protein, is a protein in humans that is encoded by the HFE gene. The primary mode of action of HFE is through the regulation of the iron storage hormone hepcidin. It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The HFE protein binds to the transferrin receptor and reduces its affinity for iron-bound transferrin.
The exact mechanism for development of HHC is not known, but there appears to be interaction of HFE with transferrin and movement of iron across epithelial surfaces. The mutant HFE does not bind properly to the transferrin receptor. Patients with HHC have very high iron stores because they absorb dietary iron at two to three times the normal rate. HHC patients accumulate iron at a rate of 0.5–1.0gm per year. Eventually, their total iron stores may exceed 50gm. Thus HHC is a disease state associated with an increased uptake of dietary iron in the presence of excessive iron in the body stores.
Symptoms of HHC usually develop after 20g of iron has accumulated in the body. Therefore, men tend to become symptomatic in their 40s, and women, because of increased iron loss from menstruation in reproductive years, become symptomatic after menopause. Alcohol consumption can accelerate the effects of iron overload. Chronic alcoholics can exhibit hepatic fibrosis or cirrhosis almost twice as frequently as nonalcoholic men. About 10% of alcoholics with cirrhosis have extensive iron deposition. The iron deposition associated with chronic alcoholism, however, is typically limited to the liver and not seen extensively in other organs.
Iron deposition in many organs occurs and the excess iron affects organ function, presumably by direct toxic effect. Excessive iron stores exceed the body’s capacity to chelate iron, and free iron accumulates. This unbound iron promotes free radical formation in cells, resulting in cellular injury. This increased iron deposition in specific tissues (hemosiderosis) and organs, particularly affects tissues and organs. It affects the skin, causing skin pigmentation; the lungs, causing pulmonary hemorrhage; the liver, causing cirrhosis; the pancreas, causing diabetes; the kidney, causing renal failure; the joints, causing polyarthritis; the gonads, causing hypogonadism; and the heart, causing cardiomyopathy. Irreversible multiple organ damage ultimately occurs. Lungs and kidneys are especially affected. Severe pulmonary hemorrhage can deplete the iron leve/>