Hemoglobin C

Source: Wikipedia, the free encyclopedia.
Hemoglobin C
SpecialtyHematology Edit this on Wikidata

Hemoglobin C (abbreviated as HbC) is an abnormal

sickle cell anemia) and the gene for hemoglobin C; this state is called hemoglobin SC disease, and is generally more severe than hemoglobin C disease, but milder than sickle cell anemia.[2]

HbC was discovered by Harvey Itano and James V. Neel in 1950 in two African-American families. It has since been established that it is most common among people in West Africa. It confers survival benefits as individuals with HbC are naturally resistant to malaria caused by Plasmodium falciparum, albeit incompletely.

Symptoms and signs

People with one copy of the gene for hemoglobin C (termed

gallstones that require treatment.[5] Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells.[6]

Red blood cell abnormalities

The red blood cells of people with hemoglobin C disease are usually abnormally small (

microcytic) with a high mean corpuscular hemoglobin concentration (MCHC). The high MCHC is caused by a decreased concentration of water inside the cells. Target cells, microspherocytes, and HbC crystals can be seen on microscopic examination of blood smears from homozygous patients.[2]

Combinations with other conditions

target cells
and few sickle cells

HbC can combine with other abnormal hemoglobins and cause serious hemoglobinopathies. Individuals with sickle cell–hemoglobin C (HbSC), have inherited the gene for sickle cell disease (HbS) from one parent and the gene for hemoglobin C disease (HbC) from the other parent. Since HbC does not polymerize as readily as HbS, there is less sickling in most cases. There are fewer acute vaso-occlusive events and therefore in some cases fewer sickle cell crises. The peripheral smear demonstrates mostly target cells, occasional hemoglobin C crystals, and only a few sickle cells. However, persons with hemoglobin SC disease (HbSC) have more significant retinopathy, ischemic necrosis of bone, and priapism than those with pure SS disease.[2]

There are also a few cases of HbC in combination with HbO, HbD and beta thalassemia.[1]

Genetics

Hemoglobin C is produced when a point mutation in the

β-globin chain of the hemoglobin. The mutation can be homozygous, occurring on both the chromosomes (alleles), or heterozygous, affecting only one allele.[1] Under heterozygous condition, people are said to have hemoglobin C trait, or as hemoglobin C carriers, and they have one gene for HbC with either one HbA gene or HbS gene. Their red blood cells contain both hemoglobin C and either normal hemoglobin A or hemoglobin S. Hemoglobin C mutation is an autosomal recessive disorder that results from the biparental inheritance of the allele that encodes for hemoglobin C.[6] If both parents are carriers of hemoglobin C, there is a chance of having a child with hemoglobin C disease. Assuming both parents are carriers, there is a 25% chance of having a child with hemoglobin C disease, a 50% chance of having a child who is a carrier of hemoglobin C, and a 25% chance of having a child who is neither a carrier nor affected by hemoglobin C disease.[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.[1]

Resistance to malaria

Individuals with HbC have reduced risk of P. falciparum malaria infection.

PfEMP1.[12] Evidences indicate that HbC reduced the level of PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite.[13] It has been predicted that with the trend of HbC mutation and falciparum prevalence, HbC would replace HbS in central West Africa in the future.[10]

Diagnosis

Physical examination may show an enlarged spleen. Tests that may be done include:

peripheral blood smear.[5]

Prevention

Genetic counseling may be appropriate for high-risk couples who wish to have a baby.[14]

Treatment

Usually no treatment is needed.

Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia [14]

Prognosis

Overall, hemoglobin C disease is one of the more

hemoglobinopathies.[6] Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia. Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain.[6] People with hemoglobin C disease can expect to lead a normal life.[14]

Epidemiology

Hemoglobin C is found most abundantly in areas of West Africa, such as Nigeria, where

African-Americans[4] while 8% of African-Americans have hemoglobin S (Sickle) gene. Thus Hemoglobin SC disease is significantly more common than Hemoglobin CC disease. The trait also affects people whose ancestors came from Italy, Greece, Latin America, and the Caribbean region.[4] However, it is possible for a person of any race or nationality to have hemoglobin C trait. 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.[3] Hemoglobin C disease is present at birth, though some cases may not be diagnosed until adulthood. Both males and females are affected equally.[6]

History

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.[20][21] Five of the ten individuals indicated sickled RBCs. But the condition was harmless as the individuals had no anaemia. Thus, it was not clear whether it was involved in sickle cell disease. Genetically, the abnormal hemoglobin was only in heterozygous condition.[22] The next year, Neel and his colleagues established that the hemoglobin is associated with sickle cell disease.[23]

The hemoglobin was named hemoglobin III,[24] but hemoglobin C was eventually used.[25][26] By 1954, it was found that the mutant hemoglobin was highly prevalent in West Africa.[27][28] In 1960, Vernon Ingram and J. A. Hunt at the University of Cambridge discovered that the mutation was a single amino acid replacement of glutamic acid with lysine.[29]

References

  1. ^
    PMID 32644469, retrieved 2020-10-26  This article incorporates text available under the CC BY 4.0
    license.
  2. ^
    PMID 12818227
    .
  3. ^
    PMID 15215497
    .
  4. ^ a b c d "Hemoglobin C Trait". Stjude.org. Retrieved 2015-03-03.
  5. ^ a b "Updating PubMed Health - National Library of Medicine - PubMed Health". Ncbi.nlm.nih.gov. 2014-11-12. Retrieved 2015-03-03.
  6. ^ a b c d e Hemoglobin C Disease at eMedicine
  7. ^
    PMID 22445352
    .
  8. PMID 26019283
    .
  9. PMID 20231425
    .
  10. ^
    S2CID 4360808
    .
  11. PMID 22445352
    .
  12. S2CID 4412263
    .
  13. PMID 22634344
    .
  14. ^ a b c MedlinePlus Encyclopedia: Hemoglobin C disease
  15. S2CID 24734397
    .
  16. PMID 12480691
    .
  17. JSTOR 2793520
    .
  18. S2CID 31674765
    .
  19. S2CID 44763460
    .
  20. PMID 13362221
    .
  21. PMID 4912473
    .
  22. PMID 14808148
    .
  23. PMID 14886398
    .
  24. PMID 13192193
    .
  25. doi:10.1182/blood.V8.11.1008.1008
    .
  26. PMID 13275117
    .
  27. PMID 13187564
    .
  28. JSTOR 2793520
    .
  29. PMID 13716852
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Hemoglobin_C&oldid=1140442569"