Makindo Medical Notes.com

Carriers of a G6PD mutation may be partially protected against malaria

About

• G6PD deficiency leads to a vulnerability to oxidative damage to the cell membrane
• Heterozygotes seem to obtain some protection against falciparum malaria
• Inherited as an X linked recessive

Epidemiology

• Common in Africa, the Mediterranean and the Middle and Far East.
• 400 million people worldwide affected

Aetiology

• There is a defect in the hexose monophosphate shunt
• There is therefore a lack of reduced glutathione
• There is a reduction in NADPH (reduced form of NADP)
• NADPH needed to maintain the iron atoms of haemoglobin in the ferrous state and to prevent membrane lipid peroxidation.

Genetics

• Mutation seen in 10% of some world populations with over 400 subtypes
• Gene is on the X chromosome and so affects males and is carried by females.
• G6PD deficiency will be present in all (homozygous) males who carry an affected X chromosome.
• Females only affected due to homozygous or extreme Lyonisation

Precipitants of Haemolysis

• Haemolysis precipitated by the oxidative crisis due to
• Drugs: e.g. primaquin, sulfonamides, Ciprofloxacin, quinidine, probenecid
• Food: fava bean ingestion or illness can provoke haemolysis - favism.
• Diabetic ketoacidosis

Complications

• If the deficiency is severe, profound haemolysis may lead to haemoglobinuria and acute kidney injury.

Clinical

• Acute haemolysis e.g. Favism, Neonatal jaundice, Anaemia, pale, jaundice, dark urine, fatigue, Shortness of breath, and a rapid heart rate. Onset is usually 2-4 days after ingestion of drug or fava beans
• Drug induced haemolysis due to Infection, Antimalarials e.g. quinine, sulphonamides, Favism, Aspirin
• Chronic haemolysis is seen

Investigations

• FBC: anaemia, increased reticulocytes
• Urine: The jaundice of haemolysis is pre-hepatic, and the bilirubin is unconjugated and therefore does not appear in the urine. Any dark urine is due partly to haemoglobinuria and partly to increased urobilinogen, which oxidises and darkens on standing
• Blood film: polychromasia, irregularly contracted and bitten-out red cells.
• Haemolysis: Raised bilirubin and LDH and low haptoglobins
• Schumm's test is positive due to methaemalbumin
• Low levels of G6PDH assay level of the red cells but can be normal in a crisis so if suspicious repeat at later date
• DAT test is negative for immune-mediated red cell destruction
• Intravascular haemolysis - Blood film shows Bite cells, Blister cells, Polychromasia, Reticulocytosis, Heinz bodies (denatured Hb)
• G6PD assay to show G6PD deficiency.

Differential

• Exclude Malaria and Sickle cell

Management

• Avoid causative drugs, Look for and treat infections
• Monitor Hb twice daily and transfuse if needed
• Haemoglobinuria can cause AKI so watch urine output, urea and creatinine
• Supportive, remove the cause, transfusions rarely needed