Congenital atransferrinemia

Congenital atransferrinemia (also known as familial hypotransferrinemia or hereditary atransferrinemia) is an extremely rare autosomal recessive disorder caused by mutations in the TF gene, which encodes transferrin — the primary iron-transport protein in the blood. Transferrin is essential for delivering iron from the intestines and storage sites to tissues throughout the body, particularly to the bone marrow for red blood cell production. In this condition, transferrin levels are severely reduced or virtually absent, leading to a paradoxical state of severe iron deficiency anemia alongside massive iron overload in non-hematopoietic tissues. The disease typically presents in infancy or early childhood with severe microcytic hypochromic anemia, failure to thrive, and growth retardation. Because iron cannot be properly transported to the bone marrow, erythropoiesis is profoundly impaired. Meanwhile, non-transferrin-bound iron accumulates in organs such as the liver, heart, pancreas, thyroid, and kidneys, leading to hemosiderosis and progressive organ damage. Hepatomegaly is common, and without treatment, patients may develop liver fibrosis, cardiac complications, and endocrine dysfunction due to iron deposition. Treatment consists of regular infusions of plasma or purified apotransferrin, which can correct the anemia and reduce iron overload by restoring normal iron transport. With appropriate transferrin replacement therapy, patients can experience significant clinical improvement, including normalization of hemoglobin levels and reduction in tissue iron stores. Iron chelation therapy may also be considered as an adjunct to manage existing iron overload. Fewer than 20 cases have been reported worldwide, making this one of the rarest inherited metabolic disorders known.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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