The most frequent cause is a mutation in the spectrin gene. Spectrin is a component of the RBC membrane, as are actin, ankyrin and protein 4.1, mutations in all of which are less frequently responsible for the condition.
About
- Autosomal dominant condition though 25% are de novo mutations
- The main result of haemolytic anaemia is the reduction of red cell half-life and anaemia
- Commonest cause of inherited haemolytic anaemia in Europe
- Seen in > 1 in 5000 but often goes undetected
Aetiology
- There is a deficiency of beta spectrin or ankyrin in the RBC cytoskeleton
- The RBC becomes more rigid alters its flexibility
- Cells are removed from the circulation mainly by the spleen
Clinical
- Haemolytic crisis precipitated by infection
- There is a great deal of variability
- Anaemia - chronic haemolysis
- Megaloblastic crises due to folate deficiency
- Splenomegaly, Jaundice, Leg ulcers, Pigment gallstones
- Aplastic anaemia can result after infection with Parvovirus B19
Investigations
- Megaloblastic anaemia often due to folate deficiency
- MCHC is usually elevated
- Increased LDH, Increased reticulocytes, DAT/Coomb's negative
- Diagnosed on Blood film + evidence of fragility when placed in hypotonic solution
- May be confirmed by flow cytometry
Management
- Oral folate supplementation 5 mg once weekly and splenectomy
- Splenectomy usually after childhood (6 years old) which reduces red cell break down and improves the lifespan of erythrocytes
- Splenectomy has a risk of pneumococcal infection and patients need to remain on Penicillin
- Hereditary elliptocytosis has a similar cytoskeleton defect but clinically is far less severe and needs no treatment
- Post splenectomy - Thrombocythemia which may be transient and may need Aspirin, Infection with encapsulated organisms. Prevention of Infection post-splenectomy
- Vaccination against Pneumococcus pre splenectomy
- Vaccination against Haemophilus Influenza type b pre splenectomy
- Meningococcal C vaccine and A vaccine to those going to endemic areas
- Penicillin V 500 mg bd possibly life long