Dyserythropoietic anemia, congenital

Congenital Dyserythropoietic Anemia
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Anemia, jaundice, splenomegaly
Complications	Iron overload, gallstones
Onset	Birth or early childhood
Duration	Lifelong
Types	N/A
Causes	Genetic mutations
Risks	N/A
Diagnosis	Blood tests, bone marrow biopsy
Differential diagnosis	N/A
Prevention	N/A
Treatment	Blood transfusions, iron chelation, bone marrow transplant
Medication	N/A
Prognosis	N/A
Frequency	N/A
Deaths	N/A

Congenital Dyserythropoietic Anemia (CDA) is a group of rare inherited blood disorders characterized by ineffective erythropoiesis, leading to anemia. The condition is marked by the presence of dyserythropoiesis, which refers to abnormal development of erythrocytes (red blood cells) in the bone marrow.

Classification

CDA is classified into several types based on clinical features, genetic mutations, and morphological characteristics of the erythroblasts in the bone marrow:

• CDA Type I: This type is caused by mutations in the CDAN1 gene. It is characterized by macrocytic anemia, binucleated erythroblasts, and chromatin bridges in the bone marrow.

• CDA Type II: Also known as HEMPAS (Hereditary Erythroblastic Multinuclearity with Positive Acidified Serum test), this type is the most common form of CDA. It is caused by mutations in the SEC23B gene. Patients exhibit normocytic anemia, multinucleated erythroblasts, and a positive acidified serum test.

• CDA Type III: This type is less common and is associated with mutations in the KIF23 gene. It is characterized by giant erythroblasts with multiple nuclei.

Pathophysiology

The pathophysiology of CDA involves ineffective erythropoiesis due to genetic mutations that affect the normal development and maturation of erythroblasts. This results in the production of abnormal red blood cells that are often destroyed in the bone marrow or shortly after entering the circulation, leading to anemia.

Clinical Features

Patients with CDA typically present with symptoms of anemia such as fatigue, pallor, and shortness of breath. Other common features include:

• Jaundice due to increased breakdown of red blood cells.
• Splenomegaly (enlarged spleen) due to increased destruction of abnormal erythrocytes.
• Iron overload due to increased intestinal absorption of iron and repeated blood transfusions.
• Gallstones due to increased bilirubin production.

Diagnosis

Diagnosis of CDA involves a combination of clinical evaluation, laboratory tests, and genetic analysis:

• Blood tests: Complete blood count (CBC) showing anemia, reticulocyte count, and serum bilirubin levels.
• Bone marrow biopsy: Examination of bone marrow aspirate to identify characteristic dyserythropoietic changes.
• Genetic testing: Identification of mutations in specific genes associated with different types of CDA.

Management

Management of CDA focuses on alleviating symptoms and preventing complications:

• Blood transfusions: To manage severe anemia.
• Iron chelation therapy: To prevent iron overload from repeated transfusions.
• Splenectomy: In some cases, removal of the spleen may be considered.
• Bone marrow transplant: This may be a curative option for some patients.

Prognosis

The prognosis for individuals with CDA varies depending on the type and severity of the condition. With appropriate management, many patients can lead relatively normal lives, although they may require lifelong monitoring and treatment.

Also see

• Anemia
• Erythropoiesis
• Bone marrow transplant
• Iron overload