NIH Rare Diseases :
52
The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1195 Definition 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. Epidemiology The prevalence is unknown. To date, there have been 16 reported cases from 14 families. Clinical description 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. Etiology 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). Diagnostic methods 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 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. Antenatal diagnosis Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutations in the family. Genetic counseling 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. Prognosis With proper treatment the prognosis is good but due to the small number of patients, long-term complications remain unknown. . Visit the Orphanet disease page for more resources.
MalaCards based summary :
Atransferrinemia, also known as
familial hypotransferrinemia, is related to
hypochromic microcytic anemia and
anemia, x-linked, with or without neutropenia and/or platelet abnormalities. An important gene associated with Atransferrinemia is
TF (Transferrin), and among its related pathways/superpathways are
Mineral absorption and
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. The drug
Iron has been mentioned in the context of this disorder. Affiliated tissues include
heart,
liver and
bone marrow, and related phenotypes are
anemia and
recurrent infections
Disease Ontology :
12
A metal metabolism disorder that is characterized by transferrin deficiency, microcytic anemia, and iron loading, and has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the structural gene for transferrin on chromosome 3q22.
OMIM :
56
Atransferrinemia is characterized by microcytic anemia and by iron loading. It can be treated effectively by plasma infusions (summary by Beutler et al., 2000).
(209300)
KEGG :
36
Atransferrinemia is a rare autosomal recessive disorder characterized by iron overload and hypochromic anemia. A few case of human atransferrinemia with mutations in the transferrin gene has been reported.
UniProtKB/Swiss-Prot :
73
Atransferrinemia: A rare autosomal recessive disorder characterized by abnormal synthesis of transferrin leading to iron overload and microcytic hypochromic anemia.
Wikipedia :
74
Atransferrinemia, not to be confused with hypotransferrinemia, is an autosomal recessive metabolic...
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Inborn errors of metabolism 
