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

• CDA III
• CDA Type 3
• Type III CDA

What is Congenital Dyserythropoietic Anemia Type 3? (Definition/Background Information)

• Congenital Dyserythropoietic Anemia Type 3 (CDA III) is a rare form of CDA characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia
• Recently, the KIF23gene (15q23) has been identified as the causal mutation for AD CDA III. This gene encodes mitotic kinesin-like protein 1 (MKLP1) which is crucial for cytokinesis
• The clinical presentation of Congenital Dyserythropoietic Anemia Type 3 is variable. CDA III can manifest with mild anemia and jaundice in neonates but it may not be discovered until childhood or adulthood
• Intensity of symptoms increases during infections, following trauma, and during pregnancy. It can also be associated with monoclonal gammopathies, multiple myeloma and retinal angioid streaks, which can lead to visual impairment
• Sporadic cases of CDA III have been associated with severe erythroid hyperplasia, skeletal disorders, intellectual deficit, and hepatosplenomegaly
• In most cases, anemia is mild and treatment is not necessary. Only during times of extreme anemia (often due to pregnancy or surgery), may a transfusion be needed. Ophthalmological follow-up is recommended in those with eye manifestations
• In most cases of Congenital Dyserythropoietic Anemia Type 3, the prognosis is good and there is no decrease in life expectancy. Quality of life may be affected in those with visual impairment

(Source: Congenital Dyserythropoietic Anemia Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Congenital Dyserythropoietic Anemia Type 3? (Age and Sex Distribution)

• The prevalence of Congenital Dyserythropoietic Anemia Type 3 is unknown. In total, about 60 cases have been reported worldwide
• Three families have been reported with autosomal dominant CDA III in Sweden, America and Argentina
• Other sporadic CDA III-like cases have been described

(Source: Congenital Dyserythropoietic Anemia Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Risk Factors for Congenital Dyserythropoietic Anemia Type 3? (Predisposing Factors)

• A positive family history may be an important risk factor, since Congenital Dyserythropoietic Anemia Type 3 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 Type 3? (Etiology)

Mutation(s) in the KIF23gene (15q23) cause Congenital Dyserythropoietic Anemia Type 3.

• This gene encodes mitotic kinesin-like protein 1 (MKLP1) which is crucial for cytokinesis 
• The KIF23 gene mutations are inherited in an autosomal manner

(Source: Congenital Dyserythropoietic Anemia Type 3; 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

What are the Signs and Symptoms of Congenital Dyserythropoietic Anemia Type 3?

The signs and symptoms of Congenital Dyserythropoietic Anemia Type 3 vary, but may include:

Very frequently present symptoms in 80-99% of the cases:

• Anemia
• Anisocytosis
• Poikilocytosis

Frequently present symptoms in 30-79% of the cases:

• Abnormal cellular phenotype
• Abnormal proerythroblast morphology
• Fatigue
• Hyperbilirubinemia
• Increased mean corpuscular volume
• Increased serum iron
• Increased total iron binding capacity

Occasionally present symptoms in 5-29% of the cases:

• Elevated hepatic transaminases
• Gingival bleeding
• Headache
• Melena
• Oral cavity bleeding
• Pallor
• Post-partum hemorrhage

The following additional signs and symptoms may be present in some affected individuals:

• Congenital hypoplastic anemia
• Hemosiderinuria
• Jaundice
• Macrocytic anemia
• Monoclonal gammopathies 
• Multiple myeloma
• Retinal angioid streaks, which can lead to visual impairment
• Skeletal disorders
• Intellectual deficits

(Source: Congenital Dyserythropoietic Anemia Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Congenital Dyserythropoietic Anemia Type 3 Diagnosed?

Congenital Dyserythropoietic Anemia Type 3 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

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 Type 3?

The complications of Congenital Dyserythropoietic Anemia Type 3 may include:

• Severe fatigue
• Fainting episodes
• Risk of infections
• Extreme anemia during pregnancy or surgeries
• Severe post-partum hemorrhage
• Iron overload
• Vision impairment

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

How is Congenital Dyserythropoietic Anemia Type 3 Treated?

• In most cases of Congenital Dyserythropoietic Anemia Type 3, anemia is mild and treatment is not necessary
• A blood transfusion may be required only during times of extreme anemia (often due to pregnancy or surgery)
• Ophthalmological follow-up is recommended in those with eye manifestations

(Source: Congenital Dyserythropoietic Anemia Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Congenital Dyserythropoietic Anemia Type 3 be Prevented?

• Currently, Congenital Dyserythropoietic Anemia Type 3 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 Congenital Dyserythropoietic Anemia Type 3?  (Outcomes/Resolutions)

• In most cases of Congenital Dyserythropoietic Anemia Type 3, the prognosis is good and there is no decrease in life expectancy 
• The quality of life may be affected in individuals with visual impairment

(Source: Congenital Dyserythropoietic Anemia Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for Congenital Dyserythropoietic Anemia Type 3:

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

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