Hemoglobin C

Hemoglobin C (HbC) is a variant of hemoglobin which is found in approximately 2-3% of African Americans and up to 8-10% of people in West Africa. It is a structural variant of the normal hemoglobin found in red blood cells. The difference between normal hemoglobin (HbA) and Hemoglobin C lies in the beta globin chain, where the glutamic acid at the 6th position is replaced by lysine due to a point mutation in the HBB gene on chromosome 11. This mutation leads to the formation of HbC instead of the normal HbA.

Genetics

Hemoglobin C is caused by a point mutation in the HBB gene that codes for the beta chain of hemoglobin. The mutation involves a change in the DNA sequence from GAG to AAG at the sixth codon of the beta-globin gene, which results in the substitution of lysine for glutamic acid in the hemoglobin protein. This genetic alteration is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to express the disease phenotype, known as Hemoglobin C disease. Individuals with only one copy of the mutation (heterozygotes) are said to have Hemoglobin C trait and usually exhibit no symptoms.

Clinical Manifestations

Hemoglobin C disease is generally milder than sickle cell disease, but it can still cause some health problems. Individuals with Hemoglobin C disease may experience mild anemia, splenomegaly (enlargement of the spleen), and increased susceptibility to infections. The symptoms are usually less severe than those associated with sickle cell disease because HbC does not lead to the same degree of red blood cell deformation and destruction.

In individuals with Hemoglobin SC disease, a condition where one inherits one sickle cell gene (HbS) and one Hemoglobin C gene, the clinical manifestations can be more severe than in Hemoglobin C disease alone but generally milder than in sickle cell anemia. Symptoms can include moderate to severe anemia, vaso-occlusive crises, and increased risk of infections.

Diagnosis

Diagnosis of Hemoglobin C and related hemoglobinopathies typically involves hematological tests such as a complete blood count (CBC) and a hemoglobin electrophoresis. Hemoglobin electrophoresis can distinguish between the different types of hemoglobin present in the blood and is crucial for diagnosing Hemoglobin C trait or disease.

Treatment

There is no specific treatment for Hemoglobin C disease. Management focuses on alleviating symptoms and preventing complications. This may include folic acid supplementation to help produce new red blood cells, vaccinations to prevent infections, and treatment of any complications that arise. Regular follow-up with a healthcare provider knowledgeable about hemoglobinopathies is important for managing the condition.

Epidemiology

Hemoglobin C is most commonly found in individuals of West African descent but can also be found in people from the Mediterranean region and in African Americans. The trait provides a selective advantage against malaria, which explains its higher prevalence in malaria-endemic areas.