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Introduction To Hemoglobinopathies

1. Haemoglobinopathies are inherited disorders of the globin chains that make up haemoglobin. They are classified as either quantitative disorders like thalassemias which result in reduced globin chain production, or qualitative disorders involving structural abnormalities in the globin chains. 2. The most common types are beta thalassemia and sickle cell disease. Beta thalassemia results from reduced or absent beta globin chain production leading to reduced haemoglobin A levels. Sickle cell disease involves a structural variant in the beta globin chain that causes red blood cells to sickle. 3. Haemoglobinopathies are diagnosed through blood tests like full blood counts, haemoglobin electrophoresis, and

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188 views

Introduction To Hemoglobinopathies

1. Haemoglobinopathies are inherited disorders of the globin chains that make up haemoglobin. They are classified as either quantitative disorders like thalassemias which result in reduced globin chain production, or qualitative disorders involving structural abnormalities in the globin chains. 2. The most common types are beta thalassemia and sickle cell disease. Beta thalassemia results from reduced or absent beta globin chain production leading to reduced haemoglobin A levels. Sickle cell disease involves a structural variant in the beta globin chain that causes red blood cells to sickle. 3. Haemoglobinopathies are diagnosed through blood tests like full blood counts, haemoglobin electrophoresis, and

Uploaded by

Michael Mazvidza
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We take content rights seriously. If you suspect this is your content, claim it here.
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Introduction to haemoglobinopathies

Normal haemoglobin
• Haemoglobin (Hb) molecules consist of four haem (iron-containing)
complexes and four globin chains (two alpha like and two beta like.
• The haem component carries oxygen and the globin chains contribute
to the stability and oxygen affinity of the Hb molecule.
Normal adult haemoglobins
Haemoglobin Globin chains % of total Hb in adult

A 2α/2β >95%

A2 2α/2δ <3.5%

F 2α/2γ <1%
Haemoglobin structure
Haemoglobinopathy
• Inherited disorders of globin chains, the protein component of haemoglobin
• Inherited haemolytic anaemias
• Inheritance is usually autosomal recessive - carriers (heterozygotes), with just one
abnormal gene, are usually asymptomatic, whereas people who inherit an abnormal
gene from both parents (homozygotes) express the disease
• Haemoglobinopathies fall into two main categories:
i. Quantitative : thalassaemias : reduced or absent production of normal α or β-globin
chains, leading to reduced levels of HbA, the main adult Hb. They are very diverse
disorders at the genetic and clinical levels.
ii. Qualitative : abnormal haemoglobins, a Hb variant results from mutations in the
genes for α or β globin chains that alter the stability or other functions of the Hb
molecule
Globin chain genes
Thalassemias
• Alpha or Beta thalassemia depending on affected gene
• Classified as thalassemia major, intermediate or minor based on
clinical severity
• Classified also as transfusion dependent thalassemia or non
transfusion dependent thalassemia based on clinical severity
Beta thalassemia
• Autosomal recessive inheritance
• Two beta genes are inherited from each parent
• Heterozygote : trait, asymptomatic
• Homozygote : May have complete absence (ß˚) or reduced amounts of beta globin chains (ß+ or ß++
)
• Complete absence implies absence of haemoglobin A- there is a compensatory increase in HBF
and HBA2
• Reduced amounts of Beta chains implies reduced amounts of HBA and relative increase in HBF
and HBA2
• Clinical presentation, depends on relative amounts of HBA produced ie. In complete absence,
severe disease, thalassemia major , transfusion dependent thalassemia
• This condition is most common in people whose ancestors originate from the Mediterranean,
Middle East, South or Southeast Asia or the Far East
Alpha thalassemia
• Autosomal recessive inheritance
• Four alpha genes inherited, two from each parent
Structural haemoglobin variants
• Group of inherited haemolytic anaemias
• Structural abnormalities in globin chains
• Abnormal physiochemical characteristics
i. Abnormal soluability
HBS : Sickle haemoglobin, Beta chain variant, sickling of red cells at low
oxygen concentrations
HBC : forms haemoglobin crystals
Common in sub Saharan Africa
Indian, Mediterranean, Asia
ii. Unstable haemoglobins
 Intracellular precipitation of haemoglobin and formation of Heinz
bodies
Results in congenital Heinz body anaemia
HBE, HB Koln
India, Mediterranean,
Asia
iii. High oxygen affinity haemoglobins
 increased O2 affinity
Poor oxygen delivery
Tissue hypoxia with secondary polycythaemia

iv. Low oxygen affinity haemoglobins


 reduced oxygen affinity
poorly oxygenated arterial blood
Cynosis

v. Inherited M-haemoglobins
Result in congenital methaemoglobunaemia
The haem iron is easily converted from Fe2+ to Fe 3+
Methaemoglobin is an inefficient HB, resultant cyanosis
Diagnosing haemoglobinopathies
• History and examination
• FBC : Red cell indices
• Special haematological investigations :
sickle cell screen
haemoglobin electrophoresis
high performance liquid chromatography
genetic mutation testing

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