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Congenital atransferrinemia is a very rare hematologic disease caused by a transferrin (TF) deficiency and characterized by microcytic, hypochromic anemia (manifesting with pallor, fatigue and growth retardation) and iron overload, and that can be fatal if left untreated.
ORPHA:1195Classification level: Disorder
The prevalence is unknown. To date, there have been 16 reported cases from 14 families.
Disease onset usually occurs in infancy or early childhood. Only one reported patient was diagnosed at the age of 20. The presenting manifestations are those of anemia such as fatigue, anorexia, irritability, tachycardia, systolic murmur and pallor. Growth retardation, hepatomegaly and recurrent infections are other frequent manifestations of the disease. In undiagnosed individuals, iron overload can lead to liver cirrhosis, heart failure and arthropathy. Hypothyroidism and splenomegaly have also been reported separately in two isolated cases. Death can occur due to congestive heart failure or pneumonia.
Congenital atransferrinemia is due to mutations in the TF gene (3q21) encoding TF, a blood protein necessary for the proper transport of iron to the liver, spleen, and bone marrow. Without the synthesis of TF, there is a reduction of iron delivery to developing erythroid precursors in bone marrow, which results in reduced hemoglobin synthesis and consequently to anemia and iron storage in peripheral tissues (secondary hemochromatosis).
Diagnosis is based on laboratory testing indicating anemia as well as a serum TF level of less than 35mg/dl. An enlarged liver, due to hemosiderosis may be noted on clinical examination in some cases. Molecular genetic testing can identify a mutation in the TF gene, confirming the diagnosis.
Differential diagnoses include other conditions that manifest with hypotransferrinemia such as GRACILE syndrome and nephrotic syndromes (see these terms) and, in adults, those suffering from chronic alcoholism.
Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutations in the family.
Congenital atransferrinemia is inherited in an autosomal recessive manner and genetic counseling is available.
Management and treatment
There is no cure for congenital atransferrinemia. Treatment usually involves monthly phlebotomies followed by infusions of whole plasma or purified apotransferrin which remove excess iron and replenish TF levels, allowing for the proper formation of hemoglobin. Treatment is life-long and regular follow-up is recommended.
With proper treatment the prognosis is good but due to the small number of patients, long-term complications remain unknown. .
A summary on this disease is available in Deutsch (2013) Español (2013) Français (2013) Italiano (2013) Nederlands (2013) Russian (2013, pdf)