Hemoglobinopathy

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Hemoglobinopathy

• John Matthews and Dilys Rapson

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Hemoglobin structure
ß
a
ß
a
heme
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Hemoglobins in normal adults
a
a
a
ß
d
?
a
a
a
ß
?
d
HbA
HbF
HbA2
98
1
lt3.5
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Hemoglobin structure
ß
a
ß
a
heme
6
Heme
7
Globin
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The Oxygen Dissociation Curve
pAO2
pVO2
normal e.g. a2ß2
abnormal e.g. ß4
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Hemoglobin synthesis
25
25
48
1.5
0.5
a
a
ß
d
?
ß
d
?
a
a
25
25
48
1.5
0.5
Chromosome 16
Chromosome 11
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Hemoglobinopathydefinition

• An inherited mutation of the globin genes
  leading to a qualitative or quantitative
  abnormality of globin synthesis

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Structural hemoglobinopathy
Amino acid substitution in the globin chain e.g.
sickle hemoglobin (HbS)
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The Thalassemias
Syndromes in which the rate of synthesis of a
globin chain is reduced beta thalassemia -
reduced beta chain synthesis alpha thalassemia
reduced alpha chain synthesis
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• Sickle Cell Anemia (HbSS)
• ß6 glu to val
• tactoids at low oxygen tension
• sickled red cells
• small blood vessel occlusion
• tissue infarction

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Sickle Cell Anemia blood film
Sickle Cells
Erythroblasts
Howell-Jolly Body
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Sickle Cell Anemia EM of red cell showing
tactoids
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Sickle cell anemia clinical features

• Hemolysis
• Occlusion of blood vessels by sickled red cells

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Sickle Cell Anemia - treatment

• Opiates and hydration for painful crises
• Pneumococcal vaccination
• Retinal surveillance
• Hydroxyurea
• Transfusion for serious manifestations
• Stem cell transplant
• Support, folate, iron chelation

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Sickle Cell Trait

• Heterozygous state for HbS (HbAS)
• No serious clinical consequences
• Sudden death during intensive training
• Hematuria, isosthenuria (renal papillary necrosis)

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Beta thalassemia

• Impaired production of beta chain
• beta thalassemia minor heterozygous (or trait)
• beta thalassemia major - homozygous

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Beta thalassemia trait

• No symptoms
• Mild microcytic anemia

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Beta thalassemia major

• No beta chain produced (no HbA)
• Severe microcytic anemia occurs gradually in the
  first year of life
• Marrow expansion
• Iron overload
• Growth failure and death

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Beta thalassemia major Male 18 years
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Beta thalassemia major treatment

• Transfusion
• Iron chelation
• Stem cell transplant

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Alpha thalassemia
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Hemoglobinopathy-antenatal diagnosis

• Test partners of heterozygous or affected
  individuals
• Antenatal diagnosis from DNA obtained by
  chorionic villus sampling, or by amniocentesis