Hemoglobinopathies

Question 1

Alpha-Thalassemia

Answer 1

Inheritance: Di-genic, variable
Gene: HBA1, HBA2

Question 2

Beta-Thalassemia

Answer 2

Inheritance: Autosomal recessive
Gene: HBB

Question 3

Sickle cell anemia

Answer 3

Inheritance: Autosomal Recessive
Gene: HbSS genotype results from HBB p. E6V
(HbAA is normal)

Question 4

Hb Bart’s Hydrops fetalis

Answer 4

●Deletion of all 4 alpha-globin alleles
●Complete absence of alpha globin
●Fatal in utero (30-36 weeks)
●Splenomegaly
●Pleural/pericardial effusions
●Generalized edema

Question 5

Hemoglobin H (HbH) Disease

Answer 5

●Deletion of 3 alpha-globin alleles
●Microcytic hypochromic anemia
●Hepatosplenomegaly
●May have skeletal changes affecting facial features
●Some are severely affected and require regular blood transfusions

Question 6

Alpha-Thalassemia Minor

Answer 6

●Deletion of 2 alpha-globin alleles
●Mild microcytic hypochromic anemia
oCan be clinically mistaken for iron deficient anemia
●Two types
●Alpha-thal-1 (aa/–)
oSeen in ASIAN populations
oCis deletion of both alleles from the same chromo
●Alpha-thal-2 (a-/a-)
oSeen in AFRICAN populations
oTrans deletion of alleles from different homologous chromosomes

Question 7

Silent carrier (Alpha-Thalassemia)

Answer 7

●Deletion of 1 alpha-globin allele
●Typically asymptomatic
●May have low mean corpuscular volume (MCV)

Typically due to large deletions (del/dup analysis most efficient)

Question 8

Beta-Thalassemia Major

Answer 8

oHb So/ So
oSevere microcytic hypochromic anemia
oSplenomegaly
oSevere bone deformities
oDeath before age 20 if untreated

Treatment:
▪Periodic blood transfusions
▪Splenectomy
▪Chelation of transfusion-induced iron overload

Question 9

Beta-Thalassemia intermedia

Answer 9

oHb S+/S+ or So/S+
oAnemia
oMay need transfusions during illness or pregnancy depending on severity of anemia

Question 10

Beta-Thalassemia Minor

Answer 10

oHb So/S or S+/S
oMicrocytic anemia
oLower than normal mean corpuscular volume

Question 11

Sicle Cell Anemia

Answer 11

●Sickle-shaped red blood cells
●Chronic hemolysis
●Vaso-occlusive events (VOE) – (“sickle cell crisis”) – damage to tissues, pain, acute or chronic injury
oOften affects bones, spleen, liver, brain, lungs, kidney, and joints
●Splenic dysfunction
●Acute chest syndrome (ACS) – chest pain, fever, pulmonary infiltrate, respiratory problems, hypoxia
oMajor cause of mortality
●Dactylitis
●Stroke
●Pulmonary hypertension

Question 12

Sickle cell trait

Answer 12

●Hb AS genotype
●Usually non-symptomatic
●Extreme exertion, high altitude, or dehydration may cause VOEs
●May have higher risk for venous thromboembolism
●Protective advantage against malaria