Sideroblastic anemia is a rare blood disorder impacting the body’s ability to properly incorporate iron into hemoglobin, the oxygen-carrying protein in red blood cells. The bone marrow produces abnormal red blood cells that cannot effectively utilize available iron, which disrupts normal red blood cell formation. This affects the creation of healthy red blood cells, crucial for oxygen transport throughout the body.
Understanding Sideroblasts
Sideroblastic anemia is characterized by “ring sideroblasts” in the bone marrow. These are immature red blood cell precursors (erythroblasts) that contain abnormal iron accumulations. In ring sideroblasts, this excess iron accumulates in the mitochondria, forming a distinctive ring around the cell’s nucleus. This unique cellular feature signifies a fundamental problem with iron utilization, where iron is present but cannot be properly integrated into hemoglobin.
When stained with Prussian blue, these iron-laden mitochondria appear as blue granules. A cell is classified as a ring sideroblast if at least five such granules encircle one-third or more of the nucleus. This accumulation shows iron is stored rather than used for its intended purpose in red blood cell development. Their presence in the bone marrow is central to diagnosis.
Recognizing the Symptoms
Symptoms of sideroblastic anemia resemble other forms of anemia, stemming from reduced oxygen-carrying capacity. Common manifestations include persistent fatigue, general weakness, and shortness of breath. Headaches, heart palpitations, and a rapid heart rate may also occur.
Skin may appear pale due to low healthy red blood cells. Some patients develop an enlarged spleen or liver, and excessive iron buildup can cause bronze skin discoloration. These symptoms result from the body’s inability to deliver sufficient oxygen.
Identifying the Causes
Sideroblastic anemia has inherited (genetic) and acquired forms. Inherited forms result from genetic mutations that disrupt heme synthesis, iron-sulfur cluster biogenesis, or mitochondrial metabolism. The most common inherited type is X-linked sideroblastic anemia, caused by mutations in the ALAS2 gene, which plays a role in the initial step of heme production. Other genetic conditions, such as Pearson syndrome, can also cause it.
Acquired forms are more common and typically develop later in life. Myelodysplastic syndromes (MDS), bone marrow disorders, are a frequent cause, especially refractory anemia with ring sideroblasts (RARS). Certain drugs, such as the antibiotics isoniazid, chloramphenicol, and linezolid, can induce sideroblastic anemia by interfering with heme synthesis or mitochondrial function. Exposure to toxins like lead or arsenic, and nutritional deficiencies, specifically copper or vitamin B6, are also recognized causes. Excessive alcohol consumption is the most common cause of acquired reversible sideroblastic anemia.
Diagnosing the Condition
Diagnosis typically begins with a complete blood count (CBC), indicating anemia and red blood cell abnormalities. However, a definitive diagnosis requires a bone marrow examination (biopsy and aspiration). During this, healthcare professionals look for characteristic ring sideroblasts, visible under a microscope after specific staining.
Iron studies assess iron levels and metabolism, often showing normal or elevated iron stores, distinguishing it from iron deficiency anemia. Genetic testing identifies specific mutations in suspected inherited cases. For acquired forms, screening for underlying conditions, drug exposures, or nutritional deficiencies is part of the diagnostic workup.
Approaches to Treatment
Treatment for sideroblastic anemia is tailored to its cause and severity. For certain inherited forms, especially X-linked sideroblastic anemia, vitamin B6 (pyridoxine) supplementation can be effective in improving hemoglobin levels. However, pyridoxine is not universally effective, and its utility in acquired forms varies.
Iron chelation therapy is often necessary for iron overload, a common complication from ineffective iron utilization or frequent blood transfusions. Medications like deferoxamine or deferasirox remove excess iron from the body. Blood transfusions alleviate severe anemia symptoms but can contribute to iron overload. For cases linked to myelodysplastic syndromes, treatments may include growth factors, immunosuppressants, or stem cell transplantation. If an acquired cause (e.g., drug, toxin) is identified, removing it can resolve the anemia.