Handbook of Genetic Counseling/Hemoglobin C

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 Testing 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) Psychosocial concerns 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 References 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. Web resources www.sicklecelldisease.org -- Sickle Cell Disease Association of America http://sickle.bwh.harvard.edu/menu_sickle.html -- basic information about hemoglobin etc. Notes The information in this outline was last updated in 2002.