Evaluation and diagnosis of sideroblastic anemia

RBC: red blood cell; MCV: mean corpuscular volume; SIFD: sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay; XLSA/A: X-linked sideroblastic anemia with ataxia; MLASA: myopathy, lactic acidosis, and sideroblastic anemia; mtDNA: mitochondrial DNA; TRMA: thiamine-responsive megaloblastic anemia; INH: isoniazid; MDS/MPN: myelodysplastic syndrome/myeloproliferative neoplasm.

* The MCV is most accurate before transfusions are given. Normocytic RBCs from transfused blood can mask microcytosis. Microcytosis generally refers to an MCV below the lower limit of normal for the laboratory (approximately 80 fL in most laboratories), but there is no strict cutoff.

Δ When more than one gene is listed, the order of listing generally reflects the likelihood of finding a pathogenic variant (more common listed first). Testing can be done using a gene panel or sequentially, depending on individual factors. If a familial disease variant is known, that specific variant can be tested. If classic syndromic features are present, initial testing can be restricted to the genes associated with the specific syndrome. Specific syndromes listed in the inset box include:

• SIFD: sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay
• XLSA/A: X-linked sideroblastic anemia with ataxia
• MLASA: myopathy, lactic acidosis, and sideroblastic anemia
• Pearson syndrome
• TRMA: thiamine-responsive megaloblastic anemia

◊ Examples of implicated medications include chloramphenicol, linezolid, and cytotoxic chemotherapy drugs associated with therapy-related MDS.