Red cell enzymopathies

Red cell enzymopathies

Red cell enzymopathies


Glucose-6-phosphate deficiency


§   G6PD is involved in the pentose phosphate shunt

§        Failure to generate adequate NADPH, results in insufficient glutathione

§        Renders red cells susceptible to oxidation

§        Denatured Hb forms heinz bodies and gets taken out by spleen

§   XLR

§   Affects males mainly

§   Female carriers have 50% normal G6PD activity (phenotype depends on degree of lyonisation)

§   West Africa, Southern Europe, Middle East, South East Asia



§   Wild type G6PD B

§        4 classes of severity depending on the level of enzyme activity relative to G6PD B

§        At least 127 different variants

§        The 3 most common variants are

§        G6PD-A(-) is common in Africa – class III 10- 60% of normal activity

§        Mediterranean variant – class II  <10% activity

§        Canton variant – class II

§   Decreased enzyme activity in aged cells

§   Survival advantage with P falciparum





Neonatal jaundice


Acute exacerbations



Class I

Eg. Santiago de Cuba

Severe – enzyme activity <10%




Class II

Eg. Mediterannean/ canton






Class III

West Africa (G6PD A-)USA

Moderate 10-60%




Class IV

Polymorphisms that do not affect enzyme activity






Clinical features

1. Neonatal Jaundice

§   Class I, II and III variants

§   Potential kernicterus

§   Starts in utero but becomes clinically apparent on day 2 or 3

§   Anaemia is not a feature

§   Manifestation of liver enzyme deficiency and underdevelopment of neonatal liver function

§   Phototherapy or exchange transfusion


2. Chronic non spherocytic haemolytic anaemia

§   Tends to occur in more severely affected (class I)

§   Extravascular haemolysis


3. Acute episodes of intravascular due to:

§        Infection

§        Drugs (dose related)

§        Antimalarials (Primaquine, ? chloroquine)

§        Aspirin (<1g/day normally ok)

§        Antibiotics (Quinolones, nitrofurantoin, sulphonamides eg septrin)

§        Dapsone

§        Fava beans

§   Haemolysis increases 1-3 days after infection/ ingestion of the drug and peaks at 7-10 days

§   Associated with back and abdominal pain

§   Urine becomes dark

§   Haemolysis is typically self limiting (severity related to dose of drug ingested but large amount of heterogeneity)

§   Favism more rapid onset (hours) and can be much more severe, with shock and can be fatal.  Due to divicine which is not present in peas and other beans.


§   May present as neonatal jaundice with kernicterus (largely only in Mediterranean children)



§        Heinz bodies in red cells (methyl violet stain)

§        Ghost cells

§        Spherocytes and fragments in film if severe haemolysis

§        Reticulocytosis / reduced haptoglobins / raised LDH / unconjugated bilirubin / DAT –ve

§        Assay for G6PD (NB can be difficult in acute haemolysis since reticulocytes have increased levels of the enzyme)

§        Screening tests eg methaemoglobin reduction test – detect levels below 30%

§        Enzyme quantifictation – spectrophotometry

§        Demostration of G6PD deficient cells with staining (normal = all cells stained)



§   Avoid triggers

§   Transfusion if severe haemolysis

§   IV fluids to reduce renal failure in severe haemolysis

§   Folic acid

§   Splenectomy may be helpful in recurrent haemolysis



Pyruvate kinase deficiency

§   Autosomal recessive

§   Pyruvate kinase is an enzyme in the glycolytic pathway

§   Glycolytic pathway generates ATP for the erythrocyte

§        Maintains membrane integrity, ferrous Hb and oxygen affinity

§   Reduced ATP, 2,3 DPaccumalation leading to right shift of the Hb dissociation curve

§        2,3-Diphosphoglycerate


Clinical features

§   Variable chronic haemolysis

§   May be apparent in the neonate if severe but often presents in later life

§   Prone to aplastic crises due to parvovirus B19



§   Reticulocytosis / raised LDH / reduced haptoglobins / variable anaemia / acanthocytes

§   PK assay



§   Folic acid

§   Transfusion during severe crises

§   Splenectomy if high transfusion requirements


substrate_____other enzymes (left)______→ 2,3-DPG _____pyruvate kinase (right)_____→ ATP



Other red cell enzymopathies – glycolytic pathway

1.    Hexokinase deficiency

2.    Glucose phosphate isomerase deficiency

3.    Phosphofructokinase deficiency

4.    Aldolase deficiency

5.    Triosephosphate isomerase deficiency (TPI)

6.    Phosphoglycerate kinase deficiency (X-linked)


§   All Autosomal recessive

§   Prevalence < 1 / million


Clinical features

§   Similar to PK deficiency although most are more severely affected for the degree of anaemia (glycolytic block results in reduced 2,3 DPG and left shift of the Hb dissociation curve)


§   TPI also causes progressive paraparesis with most dying due to cardiac arrhythmias age <5

§   PFK deficiency is associated with myopathy and exertional rhabdomyolysis which may result in renal failure



§   Morphology non specific (anisocytosis, macrocytosis and polychromasia)

§   Assay of enzyme at reference lab



§   Folic acid

§   Transfusion as necessary (beware of iron overload)

§   Splenectomy controversial



Nucleotide metabolism – pyramidine 5 nucleotidase deficiency

§   Autosomal recessive

§   Lead poisoning causes acquired deficiency


Clinical features

§   Moderate anaemia (Hb 10)

§   Reticulocytosis etc

§   Splenomegaly


§   Prominent basophilc stippling

§   Diagnosed with pyrimidine 5 nucleotidase assay

§   Treatment - symptomatic