Hereditary Acquired Anaemia
Content
• Hereditary acquired anaemia
• Pathophysiology and clinical
features
• Pathogenesis
• Haemoglobinopathies
Objective
At the
end of the PDF Notes, the students will be able to
• Explain hereditary acquired anaemia
• Describe the pathophysiology and
clinical features of Hereditary Spherocytosis
• Explain the pathogenesis of
hereditary disorders of red cell interior
• Explain haemoglobinopathies
Hereditary Acquired Anemia
• Hereditary haemolytic anaemias are
usually the result of intracorpuscular defects.
• Classified into 2 groups:
1) Hereditary abnormalities of red cell
membrane
2)
Hereditary disorders of the interior of the red cells
A. Hereditary Abnormalities of Red Cell Membrane
3 important
types of inherited red cell membrane defects:
1)
Hereditary spherocytosis
2)
Hereditary elliptocytosis (hereditary ovalocytosis)
3)
Hereditary stomatocytosis.
Hereditary Spherocytosis
Pathogenesis
• The molecular abnormality in
hereditary spherocytosis is a defect in proteins which anchor the lipid bilayer
to the underlying cytoskeleton.
1) Spectrin deficiency: deficiency in the structural protein
of the red cell membrane, spectrin
• Mutation in spectrin- α−spectrin-
severe anaemia
• Mutation by β-spectrin results
in mild Anaemia.
2)
Ankyrin abnormality: defect
in ankyrin, protein that binds protein 3 and spectrin
CLINICAL FEATURES
• 1. Anaemia is usually mild to moderate.
• 2. Splenomegaly is a constant
feature.
• 3. Jaundice occurs due to
increased concentration of unconjugated (indirect) bilirubin in the plasma
(also termed congenital haemolytic jaundice).
• 4. Pigment gallstones are
Hereditary Elliptocytosis (Hereditary Ovalocytosis)
• It is autosomal dominant disorder
involving red cell membrane protein spectrin.
Hereditary Stomatocytosis
• Stomatocytes are cup-shaped RBCs
having one surface concave and the other side as convex.
• This causes a central slit-like or
mouth-like appearance of red cells.
• The underlying defect is in membrane
protein stomatin
B. Hereditary Disorders of Red Cell Interior
• Inherited disorders involving the
interior of the red blood cells are classified into 2 groups:
1. Red
cell enzyme defects (Enzymopathies): These cause defective red cell metabolism
involving 2 pathways
i)
Defects in the hexose monophosphate shunt
ii)
Defects in the Embden-Meyerhof (glycolytic) pathway
2.
Disorders of haemoglobin (haemoglobinopathies):
These are
divided into 2 subgroups:
i)
Structurally abnormal haemoglobin: Examples are sickle syndromes and other
haemoglobinopathies.
ii) Reduced globin chain synthesis: Common
examples are various types of thalassaemias.
Red Cell Enzyme Defects (Enzymopathies) G6PD Deficiency
• Defects in hexose monophosphate
shunt- G6PD deficiency
• G6PD gene is located on the X chromosome - affecting males
PATHOGENESIS
PK Deficiency
• Pyruvate kinase (PK) deficiency is
the only significant enzymopathy of the Embden-Meyerhof glycolytic pathway.
• The disorder is inherited as an
autosomal recessive pattern. Heterozygote state – asymptomatic
• Homozygous individual presents during early childhood with anaemia, jaundice and splenomegaly.
Haemoglobinopathies
• Haemoglobin in RBCs may be
abnormally synthesised due to inherited defects. These disorders may be of two
types:
1) Qualitative disorders in which there is structural
abnormality in synthesis of haemoglobin e.g. sickle cell syndrome, other
haemoglobinopathies.
2)
Quantitative disorders in which there quantitatively decreased globin chain synthesis of
haemoglobin e.g. thalassaemias.
Summary
Ø Important types of inherited red
cell membrane defects:
1)
Hereditary spherocytosis
2)
Hereditary elliptocytosis (hereditary ovalocytosis)
3)
Hereditary stomatocytosis
• Hereditary spherocytosis is a common
type of hereditary haemolytic anaemia- defect in proteins which anchor the
lipid bilayer to the underlying cytoskeleton
• Hereditary elliptocytosis or
hereditary ovalocytosis is another autosomal dominant disorder involving red
cell membrane protein spectrin
• Hererditary
stomatocytes are swollen red
cells (overhydrated red cells) due to increased permeability to sodium and
potassium. The affected patients have mild anaemia and splenomegaly.
• Inherited disorders involving the interior of the red blood cells are classified into 2 groups: Red cell enzyme defects (Enzymopathies) and disorders of haemoglobin (haemoglobinopathies)
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