TFR2-related hemochromatosis

TFR2-related hemochromatosis, also known as hemochromatosis type 3, is a rare inherited iron overload disorder caused by mutations in the TFR2 (transferrin receptor 2) gene. It belongs to the group of hereditary hemochromatosis conditions and is classified under Orphanet code 225123. The TFR2 protein plays a critical role in sensing iron levels in the body and regulating hepcidin, the master hormone of iron homeostasis. When TFR2 is dysfunctional, hepcidin production is inappropriately low, leading to excessive intestinal iron absorption and progressive iron accumulation in tissues and organs. The disease primarily affects the liver, heart, pancreas, joints, and endocrine organs. Key clinical features include hepatomegaly, liver fibrosis or cirrhosis, elevated serum ferritin and transferrin saturation, cardiomyopathy, diabetes mellitus (sometimes called "bronze diabetes" due to associated skin hyperpigmentation), arthropathy, and hypogonadism. The clinical presentation closely resembles classic HFE-related hemochromatosis (type 1), though TFR2-related hemochromatosis may present at a somewhat younger age, typically in early to mid-adulthood. Both males and females can be affected, though males may present earlier and more severely due to the absence of physiological iron losses from menstruation. Diagnosis is established through biochemical iron studies showing elevated transferrin saturation and serum ferritin, liver MRI or biopsy demonstrating hepatic iron overload, and confirmed by molecular genetic testing of the TFR2 gene. Treatment follows the same principles as other forms of hereditary hemochromatosis and centers on therapeutic phlebotomy (regular blood removal) to reduce body iron stores and prevent organ damage. When phlebotomy is not tolerated, iron chelation therapy may be considered. Early diagnosis and treatment can prevent irreversible organ damage and allow for a normal life expectancy. Dietary modifications, including avoidance of iron supplements and limitation of alcohol intake, are also recommended.

Common questions about TFR2-related hemochromatosis