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.