From the Guidelines
Sideroblastic anemia is diagnosed through a combination of blood tests, bone marrow examination, and genetic testing, with the definitive diagnostic test being a bone marrow aspiration and biopsy with Prussian blue staining to reveal characteristic ringed sideroblasts. The initial workup includes a complete blood count (CBC) which typically shows anemia with normal or elevated red cell indices 1. Peripheral blood smear examination may reveal dimorphic red cells and basophilic stippling. Additional laboratory findings often include elevated serum iron, increased transferrin saturation, and normal or elevated ferritin levels, reflecting the paradoxical iron overload despite anemia 1.
Key Diagnostic Steps
- Complete blood count (CBC) to show anemia with normal or elevated red cell indices
- Peripheral blood smear examination to reveal dimorphic red cells and basophilic stippling
- Bone marrow aspiration and biopsy with Prussian blue staining to reveal characteristic ringed sideroblasts
- Genetic testing to identify mutations in genes like ALAS2, SLC25A38, or mitochondrial DNA, particularly in hereditary forms 1
- Evaluation for underlying conditions such as myelodysplastic syndromes, which can present with sideroblastic anemia
Importance of Early Diagnosis
Early diagnosis is crucial as treatment approaches vary depending on the specific cause, ranging from vitamin B6 supplementation to chelation therapy for iron overload 1. Unrecognized tissue iron loading might lead to severe morbidity and even mortality, underscoring the need for accurate and timely diagnosis of these disorders. Genetic testing is recommended to identify mutations in genes like ALAS2, SLC25A38, or mitochondrial DNA, particularly in hereditary forms, allowing for targeted treatment and management of the condition 1.
From the Research
Diagnosis of Sideroblastic Anemia
- Sideroblastic anemia (SA) is characterized by the accumulation of ring sideroblasts in the bone marrow due to disrupted heme biosynthesis 2.
- The diagnostic approach to SA includes a work-up for reversible causes and genetic testing for congenital SA based on clinical suspicion, family history, and genetic pedigree 2.
- There are two forms of sideroblastic anemia: congenital and acquired, with congenital SA caused by mutations in genes involved in heme biosynthesis, iron-sulfur (Fe-S) cluster biogenesis, or mitochondrial metabolism 3.
- Acquired SA is more common and can be a result of myelodysplastic syndromes (MDS) or other, generally reversible causes 2.
- Molecular analysis, including genetic testing, can contribute to the development of effective treatment for congenital and acquired sideroblastic anemia 3.
Key Features of Sideroblastic Anemia
- Ring sideroblasts are formed by disutilization and deposit of iron in the mitochondria 3.
- Congenital sideroblastic anemia has three modes of inheritance: X-linked (XLSA), autosomal recessive (ARCSA), and maternal 2.
- The most common congenital sideroblastic anemia is X-linked sideroblastic anemia caused by mutations in the erythroid-specific δ-aminolevulinate synthase gene 3.
- The most commonly acquired sideroblastic anemia is myelodysplastic syndrome with ring sideroblasts (MDS-RS), which is highly mutated in the splicing factor 3b subunit 1 (SF3B1) gene 3.