Lecture 26

Question 1

Alpha globin gene cluster is on chromosome ____ (remember there’s alpha 1 and 2.) Beta, Delta and Gamma globin gene clusters are on chromosome ___.

Answer 1

16

11

Question 2

What are the component alpha, beta, delta and gamma globin chains for Hb F, Hb A, and Hb A2? At how many months after birth does the beta chain become maximal over the gamma chain?

Answer 2

Hb F = alpha2 gamma2

Hb A = alpha2 beta2

Hb A2 = alpha2 delta2

At about 6 months.

Question 3

Remember that Hemoglobinopathies are a ______ change in hemoglobin, while Thalassemias are a ______ change in hemoglobin.

Answer 3

Qualitative

Quantitative

Question 4

Sickle Cell disease most commonly results from a point mutation in position ____ of the ____ chain and is denoted as 6Glu–> Val.

Answer 4

6

Beta

Question 5

Codocytes (aka _____ cells) are indicative of hemoglobinopathies. Their appearance is exactly as the name suggests.

Answer 5

Target cells

Question 6

Sickle cell disease will not present until infancy because it is the Hb _____ chain that comprises Hb F. Remember this changes to the ____ chain for Hb A. By 4-5 months of age, an infant with Sickle cell disease will present with hemolytic anemia that is _____cytic and _____chromic. Also remember the _____ is responsible for clearing all the damaged RBCs. Because the spleen is so heavily occupied, Sickle cell disease patients are more susceptible to _____ infections.

Answer 6

Gamma chain

Beta chain

Normocytic

Normochromic

Spleen

Bacterial

Question 7

Treatment for Sickle Cell disease involves infection prophylaxis and _________ to induce production of Hb F. Avg lifespan for these patients is between 42-47yrs.

Answer 7

Hydroxyurea

Question 8

Blood smears for patients with Sickle Cell trait will show ____ cells (codocytes) but no sickle cells.

Answer 8

Target cells

Question 9

Hb C is a hemoglobinopathy present ONLY in people of West African descent. The mutation affects the same amino acid residue as in HbS (so residue ____), but instead of Val, it converts Glu to ____. Patients with HbC will NOT exhibit change in their RBC morphology. The phenotype for this disease is less severe than HbS with less hemolysis. _____ crystals are a key feature of HbCC (homozygotes) patient blood smears.

Answer 9

6

Glu to Lys

Hexagonal crystals

Question 10

HbSC is the compound heterozygous version of Sickle Cell disease (SCD). These patients have all the symptoms of SCD, but they are less severe. What characteristic feature of the RBCs do HbSC patients show (remember it’s similar to what is found in HbC blood smears)?

Answer 10

RBCs show crystal protrusions, similar to the hexagonal crystals observed in HbC patients.

Question 11

_____ cells (codocytes) are always present in Thalassemia blood smears. Remember Thalassemias are a ____ change in Hb, so what causes the disease phenotype in these patients is the imbalance of the ratio of alpha and beta chains, rather than a structural defect in the chains themselves. Accumulation of _____ (paired or unpaired?) chains damage the RBCs.

Answer 11

Target cells

Quantitative

Unpaired

Question 12

Thalassemias result in ______ (micro, macro, or normocytic?) _______ (hyper, hypo, or normochromic?) anemia. Thalassemia _____ results from a heterozygous genotype with one normal Hb beta chain allele, and Thalassemia ____ results from the homozygous recessive genotype (these patients rely on transfusions). Keep in mind there are two mutant Beta chain alleles for Beta Thalassemia. Which one produces no Beta chain, and which one results in less Beta chain production?

Answer 12

Microcytic (smaller RBCs bc less Hb produced)

Hypochromic (less color bc less Hb produced)

Thalassemia Minor (heterozygote)

Thalassemia Major (homozygous recessive)

Beta o –> no beta chain
Beta + –> reduced beta chain production

Question 13

Infants with Thalassemia might present with ______ deformities due to a massive increase in ineffective erythropoiesis in response to _____ production from the kidneys.

Answer 13

Bone deformities

EPO

Question 14

Thalassemia major treatment includes transfusions every __-__ weeks with iron chelators. Hematopoietic stem cell transplantation is curative, but patients need a sibling donor with the same ____ (remember this is not necessary for organ transplant bc immunosuppressants can be used).

Answer 14

2-5 weeks

HLA

Question 15

___-Thalassemia is commonly associated with deletions from unequal crossing over. Characteristically, these patients show Hb ____ (the fetal form of Hb that is formed in the absence of alpha 1 and 2. It has 4 gamma chains instead.)

Answer 15

Alpha-thalassemia

Hb Barts

Question 16

There are two common haplotypes of alpha-thalassemia. Alpha o = deletion of both alpha globin and is common in ______ ___. Alpha + is a deletion of one alpha globin gene and is widely distributed (30% of _____ Americans).

Answer 16

Southeast Asia

African Americans

Question 17

_____ _____ is associated with Alpha-Thalassemia major, in which the affected individual has 0 functional copies of the alpha globin gene. These fetuses show predominantly Hb ___ (gamma chain tetramer) and experience sever anemia leading to cardiac arrest and edema. Death typically occurs in utero. This can be detected mid-gestation via ______.

Answer 17

Hydrop Fetalis

Hb Bart

Ultrasound

Question 18

Hemoglobin ___ (aka Beta 4) disease occurs in individuals with only 1 functional copy of the alpha globin gene. The beta chains form tetramers the same way gamma chains do, so the transition in production of these chains at about ___ months gestation does not alleviate the issue.

Answer 18

Hemoglobin H disease

6 months