Write about Glucose-6-phospate dehydrogenase deficiency here.
• The enzyme G6PD holds a vital position in the hexose monophosphate shunt, which oxidises glucose-6-phosphate to 6-phosphogluconate with the reduction of NADP to NADPH.
• This reaction is particularly important in red cells where it is the only source of NADPH which is used via glutathione to protect the red cell from oxidative damage.
• G6PD deficiency is a common condition that presents with a haemolytic anaemia, and affects millions of people throughout the world, particularly Africa, the Mediterranean, Middle East and South East Asia.
• Sex linked gene, carried on X chromosome, therefore affects males, carried by females, who show half the normal levels of the enzyme, and can be affected in the neonatal period or after exposure to oxidant drugs.
• Imbalanced Lyonization (X inactivation) can exaggerate the response if there is a large excess of G6PD-deficient cells in a heterozygote
• Heterozygotes are provided some protection against Plasmodium falciparum
• 400 structural types of G6PD, and mutations are mostly single amino acid substitutions
• Most common types with normal activity are called type B+, which is present in almost all Caucasians and 70% of blacks; and type A+, present in 20% of blacks.
• Many variants with reduced activity, but only TWO are common
• In the African, A-, type, the degree of deficiency is mild and more marked in older cells
• Haemolysis is self-limiting as the young red cells newly produced by the bone marrow have nearly normal enzyme activity
• In the Mediterranean type, both YOUNG and OLD RBCs have very low enzyme activity
• After an oxidant shock the Hb level may fall precipitously, and death may follow unless the condition is picked up
(that G6PD can present as)
• Acute drug-induced haemolysis (e.g. from aspirin, sulphonamides, Vit K, antimalarials)
• Favism (eating fava/broad beans)
• Chronic haemolytic anaemia
• Neonatal jaundice
• Infections and acute illnesses will also precipitate haemolysis in patients with G6PD deficiency
• Clinical features due to rapid intravascular haemolysis, with symptoms of anaemia, jaundice and haemoglobinuria
• Blood count is normal between attacks
• Haemolysis is evident
• Any offending drugs should be stopped
• Underlying infection should be treated
• Blood transfusion may be life-saving
• Splenectomy is not usually helpful.