Atransferrinemia

Atransferrinemia, also known as hypotransferrinemia, is a rare genetic disorder characterized by the absence or severe deficiency of transferrin in the plasma. Transferrin is the liver-derived protein that binds iron and transports it through the bloodstream to developing erythroid cells and other tissues. When transferrin is deficient, iron transport is impaired, leading to a paradoxical combination of iron overload in organs and ineffective iron utilization for red blood cell production.

The condition is typically inherited in an autosomal recessive manner and arises from biallelic mutations in the TF gene that encodes transferrin. In the absence of functional transferrin, iron tends to accumulate as non-transferrin-bound iron in tissues such as the liver, heart, and endocrine organs, while the delivery of iron to the bone marrow for erythropoiesis is compromised. Patients often exhibit severe, early-onset anemia and signs of iron overload, including hepatomegaly and organ dysfunction. Laboratory findings commonly show very low or undetectable serum transferrin, low transferrin saturation, and elevated ferritin.

Diagnosis relies on a combination of laboratory testing and genetic confirmation. Low or absent transferrin levels with iron overload, together with TF gene mutations, establish the diagnosis. It is important to distinguish atranstransferrinemia from other causes of iron metabolism disorders.

Management is largely supportive and based on replacing the missing transferrin and reducing tissue iron burden. Reported approaches include transfusion-based transferrin replacement or plasma transfusions to restore transferrin levels, along with iron chelation therapy to limit organ iron deposition. Regular monitoring of iron status, liver and heart function, growth, and development is essential. The rarity of the condition means treatment is guided by case reports and expert consensus rather than large clinical trials.