Clinically relevant genetic variants affecting hemoglobin

Sickle cell disease - hemoglobin polymerizes and becomes insoluble

Homozygous sickle cell disease (HbSS)

Hemoglobin SC disease

Sickle cell β thalassemia

Thalassemia - decreased production of one of the normal globin chains (alpha or beta), leading to an imbalance

Hemoglobin C disease - hemoglobin forms crystals

Hemoglobin M disease - hemoglobin iron becomes oxidized from ferrous to ferric state causing congenital methemoglobinemia

Structural variants can also have a thalassemic phenotype (Hb Lepore, Constant Spring, Hb E)

Unstable hemoglobin variants such as Hb Koln can cause congenital Heinz body hemolytic anemia

High oxygen affinity variants such as Hb Chesapeake can cause familial erythrocytosis

Low oxygen affinity variants such as Hb Kansas can cause familial cyanosis

Refer to UpToDate for details of the pathophysiology, clinical findings, and evaluation for these disorders.

Hb: hemoglobin.

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