Glucose-6-phospate dehydrogenase deficiency

Write about Glucose-6-phospate dehydrogenase deficiency here.


Aetiology


• 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


Clinical Syndromes:

(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


Ix:

• Blood count is normal between attacks

• During an attack the blood film may show irregularly contracted cells, bite cells, blister cells, Heinz Bodies and reticulocytosis

• Haemolysis is evident


Rx:

• Any offending drugs should be stopped

• Underlying infection should be treated

• Blood transfusion may be life-saving

• Splenectomy is not usually helpful.