Understanding, Diagnosing, and Using Genetic Testing for Congenital Dyserythropoietic Anemia, Type III

Expert Reviewed By: ⁠Dr. Brandon Colby MD

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Congenital dyserythropoietic anemia (CDA) is a rare group of inherited blood disorders characterized by ineffective erythropoiesis, which means the bone marrow fails to produce enough healthy red blood cells. Among the subtypes, Congenital Dyserythropoietic Anemia Type III (CDA III) is particularly unique due to its distinct clinical and genetic features. This article delves into understanding CDA III, its diagnosis, and the critical role of genetic testing in managing this condition.

What is Congenital Dyserythropoietic Anemia Type III?

CDA III is a rare genetic disorder marked by anemia, bone marrow abnormalities, and often, skeletal deformities. It is caused by mutations in the KIF23 gene, which plays a crucial role in cell division. The disorder is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene can cause the disease.

Patients with CDA III typically present with symptoms such as fatigue, jaundice, and an enlarged spleen. The severity of the symptoms can vary widely among individuals, even within the same family. In some cases, complications such as iron overload and secondary hemochromatosis can occur, necessitating careful management and monitoring.

Diagnosing Congenital Dyserythropoietic Anemia Type III

The diagnosis of CDA III involves a combination of clinical evaluation, blood tests, bone marrow examination, and genetic testing. Here’s a closer look at each step:

Clinical Evaluation

The first step in diagnosing CDA III is a thorough clinical evaluation. Physicians will look for signs and symptoms such as anemia, jaundice, and splenomegaly. A detailed family history is also essential, as CDA III often runs in families.

Blood Tests

Blood tests are crucial in diagnosing CDA III. A complete blood count (CBC) will typically show anemia with a high number of immature red blood cells (erythroblasts). Additional tests may include reticulocyte count, bilirubin levels, and iron studies to assess the degree of anemia and any associated complications.

Bone Marrow Examination

A bone marrow biopsy is often performed to examine the bone marrow’s cellularity and structure. In CDA III, the bone marrow usually shows characteristic abnormalities, including multinucleated erythroblasts and other dysplastic changes.

Genetic Testing: A Key Tool in Diagnosing CDA III

Genetic testing has revolutionized the diagnosis and management of many inherited disorders, including CDA III. Identifying the specific genetic mutation responsible for the disease can provide definitive diagnosis, guide treatment decisions, and offer valuable information for family planning.

Confirming the Diagnosis

Genetic testing can confirm the diagnosis of CDA III by identifying mutations in the KIF23 gene. This is particularly useful in cases where the clinical presentation and other diagnostic tests are inconclusive. A confirmed genetic diagnosis can also help differentiate CDA III from other types of anemia and related disorders.

Guiding Treatment Decisions

While there is no cure for CDA III, genetic testing can guide treatment decisions and management strategies. For instance, patients with severe anemia may require blood transfusions or iron chelation therapy to manage iron overload. In some cases, allogeneic hematopoietic stem cell transplantation (HSCT) may be considered, particularly in severe cases or when other treatments are ineffective.

Family Planning and Genetic Counseling

Genetic testing is also invaluable for family planning and genetic counseling. Identifying the specific mutation in a family can help predict the risk of passing the disorder to future generations. Couples with a family history of CDA III can benefit from genetic counseling to understand their reproductive options and make informed decisions.

Conclusion

Congenital Dyserythropoietic Anemia Type III is a complex and rare genetic disorder that requires a multidisciplinary approach for diagnosis and management. Genetic testing plays a pivotal role in confirming the diagnosis, guiding treatment decisions, and providing essential information for family planning. As our understanding of the genetic basis of CDA III continues to grow, so too will our ability to provide better care and support for affected individuals and their families.

For more in-depth information, you can refer to the study identifying a novel mutation in KIF23 causing CDA III in Japanese familial cases: Semantic Scholar.

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About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)