Congenital dyserythropoietic anemia (CDA) is a rare inherited blood disorder that primarily affects the production and maturation of red blood cells in the bone marrow. The hallmark of this condition is ineffective erythropoiesis, meaning the bone marrow produces red blood cells that are abnormal and often destroyed before they can function properly. This leads to anemia, which is a deficiency of healthy red blood cells or hemoglobin in the blood. The signs of CDA can vary depending on the specific type and severity, but there are several common clinical features and symptoms that often appear.
One of the most noticeable signs of CDA is **chronic anemia**, which causes persistent fatigue and weakness. Because red blood cells carry oxygen throughout the body, a shortage means tissues and organs receive less oxygen, leading to tiredness, pallor (pale skin), and sometimes shortness of breath during physical activity. This anemia is usually normochromic and normocytic, meaning the red blood cells that are present may look normal in size and color but are insufficient in number.
Another frequent sign is **jaundice**, which is a yellowing of the skin and the whites of the eyes. Jaundice occurs because the abnormal red blood cells break down prematurely, releasing excess bilirubin, a yellow pigment formed during the breakdown of hemoglobin. This buildup of bilirubin in the blood causes the yellow discoloration. Patients may also notice dark urine, which is related to the increased bilirubin being excreted through the kidneys.
An **enlarged spleen (splenomegaly)** is common in CDA. The spleen is an organ that filters blood and removes damaged or abnormal red blood cells. In CDA, because many defective red blood cells are destroyed prematurely, the spleen works harder and enlarges. This enlargement can cause discomfort or a feeling of fullness in the left upper abdomen and may contribute to further destruction of red blood cells, worsening the anemia.
Some patients experience **abdominal distension** or swelling, which can be related to an enlarged liver (hepatomegaly) or spleen. The liver may also become enlarged due to increased workload in processing the breakdown products of red blood cells.
**Growth retardation or failure to thrive** can be seen, especially in children with CDA. Chronic anemia and the body’s ongoing struggle to produce healthy red blood cells can impair normal growth and development.
Other signs include **intermittent itching (pruritus)**, which may be related to elevated bilirubin levels or liver involvement. Patients might also have a history of **recurrent infections**, which can occur if the bone marrow’s ability to produce other blood cells, like white blood cells, is affected or if the spleen’s function is compromised.
In some cases, patients may develop **iron overload** due to repeated blood transfusions or increased intestinal iron absorption as the body tries to compensate for anemia. Iron overload can cause damage to organs such as the heart, liver, and endocrine glands, leading to additional symptoms like heart palpitations, abdominal pain, or hormonal imbalances.
Physical examination may reveal **facial bone abnormalities** in certain types of CDA, such as thickening of the skull bones or other skeletal changes, although these are less common and more specific to particular subtypes.
Laboratory findings supporting the diagnosis often show **ineffective erythropoiesis** with characteristic abnormalities in red blood cell precursors seen on bone marrow examination. Peripheral blood smears may reveal **anisopoikilocytosis** (variation in red blood cell size and shape), **polychromasia** (presence of immature red blood cells), and sometimes **binucleated erythroblasts**—red blood cell precursors with two nuclei, which is a distinctive feature in some CDA types.
Patients might also have **low reticulocyt
