eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Hemoglobin C Disease

Author: Suzanne M Carter, MS, Senior Genetic Counselor, Associate, Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Montefiore Medical Center, Albert Einstein College of Medicine
Coauthor(s): Susan J Gross, MD, FRCS(C), FACOG, FACMG, Codirector, Division of Reproduction Genetics, Associate Professor, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine
Contributor Information and Disclosures

Updated: Feb 7, 2008

Introduction

Background

Hemoglobin C disease is an autosomal recessive disorder that causes mild hemolytic anemia. Considered one of the benign hemoglobinopathies, hemoglobin C disease may not be diagnosed until adulthood. Patients with hemoglobin C disease require multispecialty care.

Pathophysiology

Hemoglobin C comprises 2 normal alpha chains and 2 variant beta chains in which lysine has replaced glutamic acid at position 6. This unstable hemoglobin precipitates in red blood cells to form crystals. These intracellular crystals lead to a decrease in red blood cell deformability and an increase in the viscosity of the blood. The spleen effectively removes these crystal-containing cells.

Much like the mechanism in sickle cell hemoglobin, the amino acid change in the hemoglobin C molecule impairs malaria growth and development. It reduces parasitemia and confers protection against mild malaria attack.1,2 Therefore, persons who are heterozygous for hemoglobin C have a survival advantage in endemic areas. The risk of malaria is lower still in persons who are homozygous for hemoglobin C.

Frequency

United States

Hemoglobin C disease has a prevalence of 0.017% in African Americans.

International

In northern Africa, the prevalence of hemoglobin C disease is approximately 0.03%.

Mortality/Morbidity

Hemoglobin C disease is one of the more benign hemoglobinopathies. Some cases may not be diagnosed until adulthood.

  • Mild hemolytic anemia (see Hemolytic Anemia) may result, accompanied by a mild-to-moderate reduction in the red blood cell lifespan.
  • Persons with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain.
  • Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells. The cause of pigmented gallstones is uncertain.

Race

This condition primarily occurs in persons of African ancestry, but it has also been reported in persons of Hispanic and Sicilian ancestry.

Sex

Both sexes are affected equally.

Age

Hemoglobin C disease is present at birth.3

Clinical

History

Other than mild hemolytic anemia, most patients are asymptomatic. Symptoms can include musculoskeletal pain, retinopathy,4 cholelithiasis, and dental infarction.

  • Patients may have mild hemolytic anemia and an abnormal number of target cells.
  • Some patients may present with joint pain.
  • Retinopathy may manifest as angioid streaks, a clinical manifestation of breaks in a brittle Bruch membrane.5
    • The streaks appear as jagged, reddish-brown, subretinal lines that taper from the optic nerve.
    • Chronic hemolysis causes iron deposition in the Bruch membrane.
    • When this membrane breaks or cracks, choriocapillaries are disrupted and photoreceptor cells are lost.
    • These streaks can decrease visual activity.
  • Pigmented (bilirubin) gallstones result from excessive destruction of red cells.
  • Dental radiographs show changes to the maxilla and mandible typically associated with persistent overgrowth of erythrocyte-forming marrow, which is the basic process common to most hemolytic diseases and most hemoglobinopathies.

Physical

Except for associated angioid streaks and splenomegaly, examination findings are unremarkable.

Causes

Hemoglobin C disease is an autosomal recessive disorder that results from the biparental inheritance of the gene that encodes for hemoglobin C.

More on Hemoglobin C Disease

Overview: Hemoglobin C Disease
Differential Diagnoses & Workup: Hemoglobin C Disease
Treatment & Medication: Hemoglobin C Disease
Follow-up: Hemoglobin C Disease
Multimedia: Hemoglobin C Disease
References
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References

  1. Modiano D, Luoni G, Sirima BS, et al. Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature. Nov 15 2001;414(6861):305-8. [Medline].

  2. Rihet P, Flori L, Tall F. Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. Hum Mol Genet. Jan 1 2004;13(1):1-6.

  3. Olson JF, Ware RE, Schultz WH, Kinney TR. Hemoglobin C disease in infancy and childhood. J Pediatr. Nov 1994;125(5 Pt 1):745-7. [Medline].

  4. Hingorani M, Bentley CR, Jackson H, et al. Retinopathy in haemoglobin C trait. Eye. 1996;10 ( Pt 3):338-42. [Medline].

  5. McBrayer GM, Semes L, Stephens GG. Angioid streaks and AC hemoglobinopathy--a newly discovered association. J Am Optom Assoc. Apr 1993;64(4):250-3. [Medline].

  6. Dare FO, Makinde OO, Faasuba OB. The obstetric performance of sickle cell disease patients and homozygous hemoglobin C disease patients in Ile-Ife, Nigeria. Int J Gynaecol Obstet. Mar 1992;37(3):163-8. [Medline].

  7. Fabry ME, Kaul DK, Raventos C, et al. Some aspects of the pathophysiology of homozygous Hb CC erythrocytes. J Clin Invest. May 1981;67(5):1284-91. [Medline].

  8. Fairhurst RM, Casella JF. Images in clinical medicine. Homozygous hemoglobin C disease. N Engl J Med. Jun 24 2004;350(26):e24. [Medline].

  9. Fairhurst RM, Fujioka H, Hayton K, et al. Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state. Blood. Apr 15 2003;101(8):3309-15. [Medline].

  10. Fort JA, Graham-Pole JR, Chopik J. Vasoocclusion with homozygous hemoglobin-C disease. Am J Pediatr Hematol Oncol. 1988;10(4):323-5. [Medline].

  11. Wickramasinghe SN, Akinyanju OO, Hughes M. Dyserythropoiesis in homozygous haemoglobin C disease. Clin Lab Haematol. 1982;4(4):373-81. [Medline].

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Further Reading

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Keywords

HbC disease, mild hemolytic anemia, benign hemoglobinopathies, musculoskeletal pain, joint pain, iron deficiency, iron supplementation, angioid streaks, hemoglobin C, gallstones, pigmented gallstones, malaria, Bruch membrane, retinopathy, cholelithiasis, dental infarction, hemolysis, HbC, splenomegaly

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Contributor Information and Disclosures

Author

Suzanne M Carter, MS, Senior Genetic Counselor, Associate, Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Montefiore Medical Center, Albert Einstein College of Medicine
Suzanne M Carter, MS is a member of the following medical societies: American Bar Association
Disclosure: Nothing to disclose.

Coauthor(s)

Susan J Gross, MD, FRCS(C), FACOG, FACMG, Codirector, Division of Reproduction Genetics, Associate Professor, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine
Susan J Gross, MD, FRCS(C), FACOG, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, American Society of Human Genetics, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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