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Disease Profile

Atransferrinemia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E88.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Familial hypotransferrinemia

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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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.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
30%-79% of people have these symptoms
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection

[ more ]

0002719
5%-29% of people have these symptoms
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Abnormality of the pancreas
0001732
Arthritis
Joint inflammation
0001369
Hypothyroidism
Underactive thyroid
0000821
Percent of people who have these symptoms is not available through HPO
Abnormality of the liver
Abnormal liver
Liver abnormality

[ more ]

0001392
Atransferrinemia
0012239
Autosomal recessive inheritance
0000007
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Hypochromic anemia
0001931

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Atransferrinemia. Click on the link to view a sample search on this topic.