Paediatrics: Red blood count enzyme defect anaemias

Red blood count enzyme defect anaemias

Glucose-6-phosphate-dehydrogenase deficiency (G6PD)

·  X-linked recessive: disease occurs in heterozygous males and homozygous females, with variable expression in heterozygous females (depending on Lyonization.

·  Endemic in Mediterranean, South-East Asia, West Africa, and Middle East.

·  There are over 400 enzyme variants. African (A–) (10–60% enzyme activity) and Mediterranean (3% activity) are most clinically relevant.

·  RBC G6PD levels fall rapidly as cells age, with impaired elimination of oxidants and reduced cell integrity.

·  Intermittent acute haemolytic episodes (intravascular haemolysis) are associated with febrile infections (most common), oxidant drugs (antimalarials, sulphonamides, dapsone, aspirin, phenacetin, ciprofloxacin), foods (fava beans), chemicals (naphthalene - common in moth balls, henna).

·  May present as neonatal jaundice or chronic haemolytic anaemia.

Laboratory investigation

·  Normal during non-haemolytic state.

·  During haemolysis, findings of RBC destruction (bite cells and Hb puddling (ghost cells)), increased RBC production (raised reticulocyte count), spherocytes and Heinz bodies on blood film, DCT –ve.

·  Definitive diagnosis is by measuring reduced G6PD enzyme activity (may be falsely normal during acute haemolysis; repeat 6wks later).

Management

Avoid oxidant drugs and foods, maintain good urine output with fluids, transfuse if required, give folate supplements in chronic haemolysis or in patients recovering from acute episodes, treat hyperbilirubinaemia in newborns.

Pyruvate kinase (PK) deficiency

A rare congenital autosomal recessive (AR) condition. Chronic haemo-lytic anaemia results from deficiency of pyruvate kinase. Enzyme defi-ciency leads to ‘fall’ RBC ATP generation and ‘rise’2,3- diphosphoglycerate (DPG) production (shifts O₂ dissociation curve to right). Severity is vari-able. Neonatal jaundice is common. Patients can have persistent, severe hyperbilirubinaemia. Parvovirus B19 infection can cause (red cell) aplastic crisis. Laboratory findings are of ‘rise’RBC destruction and production, ‘fall’ PK enzyme level. Blood film pre-splenectomy not very informative.

Management

·  Oral folate supplements.

·  Blood transfusion if symptomatic anaemia.

·  Support of aplastic crisis, e.g. blood transfusion.

·  Splenectomy in severe cases.