Congenital atransferrinemia is characterized by abnormal synthesis of transferrin (TF), a plasma protein that transports iron through the blood. Lack of TF synthesis leads to reduction of iron delivery to developing erythroid precursors in bone marrow, resulting in reduced hemoglobin synthesis, as well as iron storage in peripheral tissues (secondary hemochromatosis). It is a very rare disease, described in only nine patients from seven unrelated families. Severe microcytic hypochromic anemia, growth retardation and recurrent infections are the first clinical signs of the disease. Iron overload occurs mainly in the liver, heart, pancreas, thyroid, kidney and bone joints, leading to mild to severe symptoms of liver and heart failure, arthropathy and hypothyroidism. Death may occur due to heart failure or pneumonia. Laboratory studies demonstrate severe microcytic anemia associated with very low to undetectable levels of transferrin. The mode of inheritence is autosomal recessive. Mutations in the TF gene (3q21) have been associated with this condition: compound heterozygosity for a deletion/insertion and a missense mutation was found in one of the patients. Polymorphisms in the TF gene have been associated with iron deficiency anemia in menstruating women. Treatment with infusions of plasma or purified apotransferrin may stabilize or correct the anemia and growth defects.
Last update: February 2005