12-2 L1 Genetics of RBC disorders

Question 1

Name 2 things Enzymes in the RBC provide

Answer 1

• energy
• protection (redox environemnt of the RBC)

Question 2

Name 3 general mechanisms of Anemia

Answer 2

• Decreased RBC production
• Hemolysis
• Blood loss or sequestration

Question 3

What is the most common RBC enzyme deficiencies?

Answer 3

• G6PD def

Question 4

G6PD def

• mode of inheritance
• confers a sensitivity to oxidative injury and hemolysis

Answer 4

• X-linked recessive
• Confers a sensitivity to oxidative injury and hemolysis
  
  • Intermittent anemia (drugs, infection)
  • Chronic anemia

Question 5

G6PD

• what is seen iwth A- varient
• MEditerranean variant

Answer 5

• A-: no G6PD at 120 in RBC
• MV: no G6PD in most of RBC lifespan

Question 6

What is morphologically seen with oxidant hemolysis?

Answer 6

• bite cells
• blister cells (eccentrocytes)

Question 7

What is hemoglobin composed of

• Hgb F
• Hgb A

Answer 7

• Hgb F: alpha and gamma
• Hgb A: alpha and beta

Question 8

Hemoglobinpathies

• Quantitative disorders
• Qualitative disorders

Answer 8

Hemoglobinpathies

• Quantitative disorders: thalassemia
• Qualitative disorders: sickle cell

Question 9

Provide the distribution for the following diseases

• Thalassemia
• HgS
• HgC

Answer 9

• Thalassemia (mediterrean, india and asia)
• HgS (E6V): mid africa
• HgC (lysine): east africa

Question 10

what is the most common found in

B-thalassemia

alpha-thalassemia

Answer 10

• B-t: Italian, sicilian, greek
• A-t: southeast asian

Question 11

Name two important pathophyisological causes for Thalassemia

Answer 11

• Imbalance between alpha and beta globins
• Ineffective erythropoiesis

Question 12

What type of mutations are seen with Thalassemia

• Alpha (AD)
• Beta (BC)

Answer 12

• Alpha: deletion
• Beta: mutation

Question 13

Beta thalassemia major (Cooley’s Anemia)

Answer 13

• B^o/B^o

Question 14

alpha thalassemia

• Silent carrier
• Thalassemia trait
• Hgb H disease
• Hydrops fetalis

Answer 14

• Silent carrier: aa/a-
• Thalassemia trait: –/aa
• Thalassemia trait: a-/a-
• Hgb H disease: –/a-
• Hydrops fetalis: –/–

Question 15

Risk of thalassemia major in offspring of

• trans african genotype
• cis asian genotype

Answer 15

• trans: a-/a-
  
  • no thalassemia major
• cis: –/aa
  
  • 25% thalassemia major

Question 16

Sickle cell disease

most prredominant in what top three ethnicities?

Answer 16

• AA
• Native America
• Asian

Question 17

ID the genotype and severity of the following diseases

• sickle cell anemia
• sickle Hgb C disease
• sickle Bo thalassemia
• sckle B+ thalassemia

Answer 17

• sickle cell anemia: SS 4⁺
• sickle Hgb C disease: SC 2⁺
• sickle B^o thalassemia: SB^o 4⁺
• sickle B⁺ thalassemia: SB⁺ 1-2⁺

Question 18

Name 3 catagories that are associated with sickle cell disease

Answer 18

• Chronic hemolytic anemia
• Vasoocclusive complications
• Chronic organ damage
  
  • spleen

Question 19

Diamond Blackfan Anemia

congenital or inherited pure red cell aplasia

• inheritance
• pathology

Answer 19

• Inhertitance
  
  • 60% sporadic (or familial inhertiance auto recessive)
  • 40% auto dominant (variable penetrance and expressivity)
• Pathology
  
  • disorder of eryhroid (RBC) progenitors
  • defect in production and function of ribosomes
  • increased apoptosis leading to erythroid failure

Question 20

Fanconi anemia

inherited bone marrow syndrome (aplastic anemia)

• inheritance
• pathology
• analysis

Answer 20

• autsomal recessive
  
  • FANCB is x-linked
• Disorder of hematopoietic stem cells
• DEB (diepoxybutane)