Hemoglobin variants – pathomechanism, symptoms and diagnosis

The diagnosis of hemoglobin variants that are not any of the better-known forms of thalassemia, sickle cell, HbC, HbD, or HbE anomalies is often challenging and requires detailed knowledge of the difference in symptoms and analysis. Experience in laboratory medicine plays an important role as the range of variants is extensive and lack of expertise can result in a wrong diagnosis. Hemoglobin variants with low oxygen affinity may present cyanosis and low oxygen saturation levels, whereas variants with increased oxygen affinity show polyglobulia and concomitant complications. Differential diagnosis of methemoglobin variants requires careful assessment, which can be problematic especially in pediatric medicine. Other variants, due to their instability, can cause more or less distinct hemolysis or thalassemia syndromes depicting serious disease patterns. Clear distinction is not always possible as several symptoms are often present. Many variants are autosomal dominant inherited.