Sideroblastic anaemia

Sideroblastic anaemia displays heterogeneous inheritance, reflecting its genetic diversity. The most common congenital form, X-linked sideroblastic anaemia (ALAS2), follows X-linked recessive inheritance; SLC25A38-related and several syndromic forms follow autosomal recessive inheritance, and Pearson syndrome arises from mitochondrial DNA deletions.

Recurrence risk and prenatal counselling depend on the molecular diagnosis in the family. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

The diagnosis is established by demonstration of ring sideroblasts on bone marrow aspirate, visualised by Prussian blue (Perls) staining as a perinuclear ring of iron-laden mitochondria around the erythroblast nucleus.

Following exclusion of myelodysplastic syndromes (MDS) and acquired causes (such as lead toxicity, copper deficiency, chronic alcohol use, and certain drugs), molecular genetic testing establishes the specific congenital subtype.

However, ring sideroblasts are not specific to congenital forms and may also be observed in acquired conditions, particularly myelodysplastic syndromes (MDS); therefore, clinical context and molecular genetic testing are essential for definitive classification.

• Confirming the clinical diagnosis at the molecular level, providing certainty and a defined basis for further clinical decisions.
• Informing clinical management (symptomatic treatment, multidisciplinary care and supportive measures), which represents a prerequisite for targeted medical care decided by the treating physicians in consultation with the affected individual.
• Enabling predictive testing of at-risk family members, supporting individualised genetic counselling and reproductive decision-making.

• Ogunbileje JO, Harris N, Wynn T, Kashif R, Stover B, Osa-Andrews B. ATP-binding cassette transporter of clinical significance: sideroblastic anemia. J Pers Med. 2024;14(6):636. doi:10.3390/jpm14060636. PMID: . PMCID: PMC11204910.
• Girard S, Geneviève F, Rault E, Fenneteau O, Lesesve JF. When ring sideroblasts on bone marrow smears are inconsistent with the diagnosis of myelodysplastic neoplasms. Diagnostics (Basel). 2022;12(7):1752. doi:10.3390/diagnostics12071752. PMID: . PMCID: PMC9320983.
• Jové-Solavera D, Rámila M, Ferrer-Cortés X, Olivella M, Venturi V, Morado M, et al. The role of genetic testing in accurate diagnosis of X-linked sideroblastic anemia: novel ALAS2 mutations and the impact of X-chromosome inactivation. Sci Rep. 2025;15(1):11843. doi:10.1038/s41598-025-95590-x. PMID: . PMCID: PMC11977005.