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
http://www.hopkinsmedicine.org/dnadiagnostic/betavariants.htm (lab performs complete gene sequencing and testing of known mutations once electrophoresis has been performed)
 * 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

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

Web resources

 * www.sicklecelldisease.org -- Sickle Cell Disease Association of America
 * http://sickle.bwh.harvard.edu/menu_sickle.html -- basic information about hemoglobin etc