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Figure 12.24 Peripheral blood film findings in hereditary spherocytosis.
SECTION II
Hereditary Stomatocytosis asymptomatic. Several variants of G6PD have been
Stomatocytes are cup-shaped RBCs having one surface described. The normal G6PD variant is designated as type B
concave and the other side as convex. This causes a central but blacks have normally A+ (positive) type G6PD variant.
slit-like or mouth-like appearance of red cells. The underlying The most common and significant clinical variant is A–
defect is in membrane protein, stomatin, having autosomal (negative) type found in black males. Like the HbS gene, the
dominant pattern of inheritance. The stomatocytes are A–type G6PD variant confers protection against malaria.
swollen red cells (overhydrated red cells) due to increased Individuals with A– G6PD variant have shortened red cell
permeability to sodium and potassium. The affected patients lifespan but without anaemia. However, these individuals
have mild anaemia and splenomegaly. develop haemolytic episodes on exposure to oxidant stress
such as viral and bacterial infections, certain drugs
B. HEREDITARY DISORDERS OF RED CELL INTERIOR (antimalarials, sulfonamides, nitrofurantoin, aspirin, vitamin
K), metabolic acidosis and on ingestion of fava beans
Inherited disorders involving the interior of the red blood (favism).
cells are classified into 2 groups:
PATHOGENESIS. Normally, red blood cells are well
1. Red cell enzyme defects (Enzymopathies): These cause protected against oxidant stress because of adequate
defective red cell metabolism involving 2 pathways generation of reduced glutathione via the hexose mono-
(Fig. 12.26): phosphate shunt. Individuals with inherited deficiency of
i) Defects in the hexose monophosphate shunt: Common G6PD, an enzyme required for hexose monophosphate
example is glucose-6-phosphate dehydrogenase (G6PD) shunt for glucose metabolism, fail to develop adequate
deficiency. levels of reduced glutathione in their red cells. This results
ii) Defects in the Embden-Meyerhof (glycolytic) pathway:
Haematology and Lymphoreticular Tissues
Example is pyruvate kinase (PK) deficiency.
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.
These disorders are discussed below.
Red Cell Enzyme Defects (Enzymopathies)
G6PD DEFICIENCY
Among the defects in hexose monophosphate shunt, the most
common is G6PD deficiency. It affects millions of people
throughout the world. G6PD gene is located on the X
chromosome and its deficiency is, therefore, a sex (X)-linked Figure 12.25 Osmotic fragility test in hereditary spherocytosis
trait affecting males, while the females are carriers and are showing increased fragility.