What are the other Names for this Condition? (Also known as/Synonyms)

• Congenital Atransferrinemia
• Familial Hypotransferrinemia
• Hereditary Hypotransferrinemia

What is Atransferrinemia? (Definition/Background Information)

• 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
• Disease onset usually occurs in infancy or early childhood. Only one reported patient was diagnosed at the age of 20 years
• 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 Atransferrinemia
• 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
• 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

(Source: Congenital Atransferrinemia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Atransferrinemia? (Age and Sex Distribution)

• Atransferrinemia is a rare congenital disorder, reported in only 16 individuals from 14 families
• The presentation of symptoms may occur in the neonatal period or infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Atransferrinemia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Atransferrinemia can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Atransferrinemia? (Etiology)

Atransferrinemia is caused by mutations in the transferrin gene (TF gene).

• This gene codes for the transferrin protein, which is a component of blood and essential for the transport of iron to bone marrow, liver, and spleen
• Absence of transferrin leads to reduced delivery of iron, causing decreased hemoglobin synthesis. Additionally, the iron that is not utilized gets deposited in peripheral tissues
• Atransferrinemia is inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Atransferrinemia?

The signs and symptoms of Atransferrinemia may include:

• Anemia
• Abnormality of the liver
• Abnormality of the cardiovascular system
• Arthritis
• Hypochromic anemia
• Hypothyroidism
• Recurrent infections

(Source: Atransferrinemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Atransferrinemia Diagnosed?

• The diagnosis of Atransferrinemia is based on laboratory testing indicating anemia as well as a serum transferrin 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, and in adults, those with chronic alcoholism

(Source: Congenital Atransferrinemia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Atransferrinemia?

The complications of Atransferrinemia may include:

• Delayed growth and development
• Recurrent, severe infections that cause scarring of tissue
• Pain due to arthritis
• Congestive heart failure

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Atransferrinemia Treated?

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 transferrin levels, allowing for the proper formation of hemoglobin
• Treatment is life-long and regular follow-up is recommended

(Source: Congenital Atransferrinemia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Atransferrinemia be Prevented?

Atransferrinemia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Atransferrinemia? (Outcomes/Resolutions)

• With proper treatment, the prognosis is good for Atransferrinemia 
• However, due to the small number of patients, long-term complications remain unknown

(Source: Congenital Atransferrinemia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Atransferrinemia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/