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

• CDA (Congenital Dyserythropoietic Anemia)

What is Congenital Dyserythropoietic Anemia? (Definition/Background Information)

• Congenital Dyserythropoietic Anemia (CDA) is a hereditary disease that affects the production of red blood cells (erythropoiesis) and is characterized by anemia and problems in various organs
• The signs and symptoms may include fatigue, weakness, pale skin, yellowing of the skin and eyes (jaundice), larger-than-normal liver and spleen (hepatosplenomegaly), and problems of the heart
• There are four major types of the condition. Each type has a different cause and the additional signs and symptoms mentioned below:
  • CDA Type 1: Characterized by moderate to severe anemia; jaundice; hepatosplenomegaly; and iron overload, which can lead to heart problems, liver disease (cirrhosis), and diabetes. Some people are born with skeletal defects of the fingers and/or toes. In some cases, the disease can be detected before birth as a hydrops fetalis. It is usually caused by changes (mutations) in theCDAN1 and C15orf41 (less frequently) genes 
  • CDA Type 2: Characterized by hepatosplenomegaly, gallbladder stones, and a milder form of anemia. After 20 years of age, some affected people develop iron overload. It is caused by mutations in the SEC23B gene 
  • CDA Type 3: The rarest form of the types. The liver is unaffected, but eye and blood problems (monoclonal gammopathy) are present. The exact cause of this type is currently unknown but it likely results from mutations in a gene located on the long arm of chromosome 15 at a position designated 15q22
  • CDA Type 4: Characterized by very severe anemia. It is caused by mutations in the KLF1 gene
• Types 1 and 2 are inherited in an autosomal recessive manner. Type 3 appears to be inherited in an autosomal dominant manner. Type 4 is inherited in an autosomal dominant manner
• Treatment may involve the use of a medication called interferon, and a bone marrow transplant

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

Who gets Congenital Dyserythropoietic Anemia? (Age and Sex Distribution)

• Congenital Dyserythropoietic Anemia is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Congenital Dyserythropoietic Anemia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Congenital Dyserythropoietic Anemia can be inherited

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 Congenital Dyserythropoietic Anemia? (Etiology)

There are four major types of Congenital Dyserythropoietic Anemia. Each type has a different cause and their modes of inheritance may differ as well

• CDA Type 1: Usually caused by changes (mutations) in theCDAN1 and C15orf41 (less frequently) genes, and inherited in an autosomal recessive manner
• CDA Type 2: It is caused by mutations in the SEC23B gene, and inherited in an autosomal recessive manner
• CDA Type 3: This is the rarest form of the types. The exact cause of this type is currently unknown, but it likely results from mutations in a gene located on the long arm of chromosome 15 at the position designated 15q22. It is likely to be inherited in an autosomal dominant manner
• CDA Type 4: This type of Congenital Dyserythropoietic Anemia is caused by mutations in the KLF1 gene, and inherited in an autosomal dominant manner

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

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

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 Congenital Dyserythropoietic Anemia?

The signs and symptoms of Congenital Dyserythropoietic Anemia vary depending on the type of disease.

The signs and symptoms of Type 1 Congenital Dyserythropoietic Anemia include:

• Moderate to severe anemia
• Jaundice
• Hepatosplenomegaly 
• Iron 
• Congenital skeletal defects of the fingers and/or toes. 
• Hydrops fetalis or edema in the fetus (in some cases)

The signs and symptoms of Type 2 Congenital Dyserythropoietic Anemia include:

• Hepatosplenomegaly
• Gallbladder stones
• Milder form of anemia
• Iron overload (In some affected individuals, after 20 years of age)

The signs and symptoms of Type 3 Congenital Dyserythropoietic Anemia include:

• Eye and blood problems (monoclonal gammopathy) 

The signs and symptoms of Type 4 Congenital Dyserythropoietic Anemia include: 

• Very severe anemia

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

How is Congenital Dyserythropoietic Anemia Diagnosed?

Congenital Dyserythropoietic Anemia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Prenatal examination of the fetus for signs of hydrops fetalis

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 Congenital Dyserythropoietic Anemia?

The complications of Congenital Dyserythropoietic Anemia may include:

• Severe fatigue
• Fainting episodes
• Risk of infections
• Iron overload
• Liver disease (cirrhosis)
• Diabetes
• Heart problems

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

How is Congenital Dyserythropoietic Anemia Treated?

The treatment for Congenital Dyserythropoietic Anemia may involve:

• Use of a medication called interferon
• Bone marrow transplant

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

How can Congenital Dyserythropoietic Anemia be Prevented?

• Presently, Congenital Dyserythropoietic Anemia 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), if available, 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 Congenital Dyserythropoietic Anemia? (Outcomes/Resolutions)

• The prognosis of Congenital Dyserythropoietic Anemia is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Congenital Dyserythropoietic Anemia:

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

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