Handbook of Genetic Counseling/Hemoglobin C
Overview of Hemoglobin and genes
- Hemoglobin is the protein in blood that carries oxygen and gives blood its red color
- There are hundreds of different types or variants of hemoglobin
- Hemoglobin A is the most common type of hemoglobin that is made in children and adults
- Hemoglobin C is one of the many hemoglobin variants
- The kind of hemoglobin our body makes depends on the genes we inherit
- Genes are the units of inheritance that tell our bodies how to grow and develop
- Some genes tell our bodies how to make protein chains that are essential components of hemoglobin
- One pair of genes, called beta globin, tells the body how to make one of the components of hemoglobin
- Changes in these beta globin genes can alter the instructions and can result in different types of changes in the structure of hemoglobin
- We usually get one copy of the beta globin gene from our mother and one from our father
- We know that you inherited one gene that was altered and results in the variant hemoglobin C being made
- The other gene produces the usual type of hemoglobin Hb A
- The presence of only one altered copy of the beta globin gene almost never causes symptoms or health problems for the individual (There have been rare instances where Hb C carriers have had some eye problems)
- When an individual has one altered and one unaltered copy of a gene, we say that they are carriers
Potential Risks for future offspring
- A carrier for Hemoglobin C is at an increased risk for having children with a genetic condition (Hb SC disease) similar to, but less severe than sickle cell anemia.
- Are you familiar with sickle cell anemia?
- Sickle cell anemia occurs only if a person has inherited two hemoglobin S genes, one from each parent (Hb S is another variant of the beta globin gene and is even more common than hemoglobin C)
- Symptoms of sickle cell anemia include:
- Increased susceptibility to frequent infections
- Anemia (that is not corrected with iron supplementation)
- Painful episodes caused by the blood cells blocking blood flow to body tissues
- The risks to children of a carrier are dependent on whether or not the other partner carries a hemoglobin variant
- The fact that you are a carrier for Hb C means that there may be potential risks to your children, but this is only possible if your partner has sickle cell trait or Hb C trait
- If the father of the fetus tests positive for sickle cell trait or hemoglobin C trait there is a 25% chance that the fetus will have either hemoglobin SC disease or a mild form of anemia, a 1 in 50% chance that the fetus will be a carrier like one of the parents, and a 25% chance that the fetus will make only the usual hemoglobin (type A).
Symptoms of Hemoglobin SC disease
(also called Hemoglobin C disease)
- Hemoglobin SC disease is milder than sickle cell disease
- Sometimes the symptoms don't arise until middle or late in life
- Only physical sign is an enlarged spleen in 65% of individuals with Hb SC disease
- Mild (hemolytic) anemia may result, accompanied by a mild-to-moderate reduction in the red cell lifespan
- Patients may have sporadic episodes of 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 pigment stones is uncertain.)
- Often goes unrecognized until a serious complication which may include
- blood in the urine (hematuria)
- pain in the hip where part of the leg bone tissue has died (aseptic necrosis of the femoral heads)
- eye problems (proliferative sickle retinopathy (PSR)) which can result in bleeding in the eye and retinal detachment
- In large study in Jamaica, 1/3 with Hb SC disease had PSR at varying stages
Hb C (homozygous)
- mild hemolytic anemia with splenomegaly
- red blood cells contain less water
- less deformable and are not in circulation as long
- also have a decreased oxygen affinity
- may develop gallstones
- no special treatment necessary
Incidence of sickle cell trait and Sickle cell anemia
- Sickle cell trait occurs in about 8% (or 1 in 12) African Americans
- Prevalence among Hispanics whose families originated from the Caribbean, Central America, or South America is approximately 4% (or 1 in 24)
- Carrier rate among 2 million screened over 4 years in California showed 6,921 nonblack infants had sickle cell trait ( .35% or approximately 1 in 300)
- 58 out of 2 million non black children had sickle cell disease from Calif. Newborn screen
- Carrier rate in Caucasians has been reported to be 1 in 600
Frequency of hemoglobin SC disease and Hb C trait
- In the US: Hemoglobin SC disease has an incidence of 0.017% less than 1 in 5000 n African Americans.
- Internationally: In northern Africa, the incidence of Hb C disease is approximately 0.03%.
- Hb SC disease is more common in individuals of African descent, but it also has been reported in people of Hispanic and Sicilian ancestry
- Gene frequency in African Americans is about 1 in every 100 to 1 in every 50 (1-2%)
- Gene frequencies are highest in Ghana and Upper Volta approaching about 1 in 7 (15%)
Possible to have Hb C with other beta globin variants
- Hb C and Beta Thalassemia if the Beta thal mutation is null (resulting in not functional beta chain production)
- Causes similar symptoms and problems as Hb SC disease
- Discuss ability to do simple blood test for partner to determine if they carry a Beta globin variant or Beta thalassemia so we can clarify risks for future children (hemoglobin electrophoresis with an A2 quanitiation to identify possible beta thalassemia)
- Covered by most insurance companies and can be ordered by primary care physician
- Some may require preauthorization so you may want to find out if this is necessary before ordering testing
- Direct mutation analysis by PCR possible but I will not discuss this because Hb electrophoresis should be sufficient
http://www.hopkinsmedicine.org/dnadiagnostic/betavariants.htm (lab performs complete gene sequencing and testing of known mutations once electrophoresis has been performed)
- May be nervous and think it is more serious initially
- May be a lot of information to understand at once so talk about how it will be in letter
- Guilt about possibly passing on something that could cause health problems
- Ethnic issues surrounding the higher prevalence among minority populations that have been oppressed in the past.
Other Facts about Hb C
- Hemoglobin C is composed of 2 normal alpha-chains and 2 variant beta-chains, where lysine has replaced glutamic acid at position 6
- This unstable hemoglobin is less soluble and it tends to crystallize
- Intracellular crystals lead to a decrease in red cell deformability and blood that is more viscous
- The spleen effectively removes these crystal-containing cells
- Hemoglobin C trait is not detected by solubility testing or by a sickle cell preparation.
- Heterozygotes have as much as 35% hemoglobin C
- The Metabolic and Molecular Bases of Inherited Disease (8th edition). 2001. McGraw Hill. Chapter 181 Hemoglobinopathies . Weatherall, D.J., Clegg, J.B., Higgs, D.R., Wood, W.G.
- Newborn screening for sickle cell disease: 4 years of experience from California's newborn screening program. Journal of Pediatric Hematology Oncology. 18(1): 36-41. (1996).
- De Caluwe, J P; Alexander, M; Bondue, H. Study of 19 heterozygote AC carriers and of 5 cases of double hemoglobinopathy SC. ACTA CLINICA BELGICA. vol. 48, no. 5 (1993): 297-306.
- Rana, S R; Sekhsaria, S; Castro, O L. Hemoglobin S and C traits: contributing causes for decreased mean hematocrit in African-American children. PEDIATRICS. vol. 91, no. 4 (1993 Apr): 800-802.
- www.sicklecelldisease.org -- Sickle Cell Disease Association of America
- http://sickle.bwh.harvard.edu/menu_sickle.html -- basic information about hemoglobin etc.
The information in this outline was last updated in 2002.