Transferrinemia

Transferrinemia, also known as hypotransferrinemia, is a very rare inherited disorder characterized by an absence or severe deficiency of transferrin, the main iron-binding transporter in blood.

Most cases are autosomal recessive; caused by biallelic mutations in the TF gene on chromosome 3.

In transferrinemia, iron cannot be efficiently delivered to developing red blood cells, causing anemia, typically severe and microcytic. At the same time, iron absorption continues and iron accumulates in organs as non-transferrin-bound iron, leading to hepatic, pancreatic, cardiac and endocrine iron overload.

Clinical features include early-onset anemia, hepatomegaly, growth failure, and signs of organ iron deposition (liver dysfunction, diabetes, cardiomyopathy). Serum transferrin is very low or undetectable; transferrin saturation is low; ferritin may be elevated.

Diagnosis is suspected in infants with severe microcytic anemia and evidence of iron overload, and is confirmed by markedly reduced transferrin levels and genetic testing of the TF gene.

Treatment is not standardized; reported approaches include transferrin replacement therapy (plasma transfusions or recombinant transferrin) to restore iron transport, iron chelation to reduce tissue iron load, and supportive care such as red cell transfusions when needed.

Prognosis depends on access to therapy and extent of organ involvement; without treatment, progressive iron deposition can cause organ failure.

Epidemiology: extremely rare with a small number of cases reported in the literature.