Microcytic Anemia with Low HbA2 and Normal HbA: Two Cases of Rare Thalassemia.

Thalassemia is a relatively common genetic blood disorder, diagnosed based on characteristic hemoglobin electrophoresis patterns, along with clinical and hematological findings. Here we present two siblings who were incidentally found to have persistent microcytic anemia (hemoglobin levels of 10.7 g/dL and 10.1 g/dL) despite normal ferritin levels. Initial hemoglobin electrophoresis showed an abnormal, non-diagnostic pattern with markedly reduced or absent HbA2 (0-0.9%), mildly elevated HbF (1.9-2.2%), and normal HbA (∼97%). Finally, genetic testing revealed homozygous Hb Knossos (HBB c.82G > T; p.Ala28Ser) and a concurrent homozygous delta-globin gene frameshift mutation (HBD c.179del; p.Lys60Argfs*2). These cases highlight a distinctive hemoglobin electrophoresis pattern resulting from the co-inheritance of Hb Knossos and delta-globin gene mutations and describe the phenotypic presentation of this rare thalassemia genotype. Awareness of this combination is essential to avoid misdiagnosis and underscores the importance of genetic testing in patients with unexplained microcytic anemia.