It confers survival benefits as individuals with HbC are naturally resistant to malaria caused by Plasmodium falciparum, albeit incompletely.

The anemia in hemoglobin C disease is classified as hemolytic, because it is caused by the destruction of red blood cells.

Target cells, microspherocytes, and HbC crystals can be seen on microscopic examination of blood smears from homozygous patients.

[4] This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy.

In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops.

In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia, jaundice and enlargement of spleen.

[12] Evidences indicate that HbC reduced the level of PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite.

Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia [14] Overall, hemoglobin C disease is one of the more benign hemoglobinopathies.

[14] Hemoglobin C is found most abundantly in areas of West Africa, such as Nigeria, where Yorubas live.

The trait also affects people whose ancestors came from Italy, Greece, Latin America, and the Caribbean region.

In terms of geographic distribution, the hemoglobin C allele is found at the highest frequencies in West Africa, where it has been associated with protection against malaria.

[6] Studying the molecular basis of sickle cell disease, Linus Pauling and Harvey Itano at the California Institute of Technology discovered in 1949 that the disease was due to abnormal hemoglobin called HBS.

[18][19] In 1950, Itano and James V. Neel discovered from two African-American families a different blood condition very similar to sickle cell disease.