Haemoglobinopathy Flashcards
Explain the normal structure of adult haemoglobin
- 2 alpha globin chains
- 2 beta globin chains
- each chain has a haem group (porphyrin ring + iron)
What chromosome is the alpha chain found in and how many copies?
- chromosome 16
- 2 genes per chromosome
- 4 per cell
What chromosome are beta chains found in and how many copies?
- chromosome 11
- 1 copy per chromosome, 2 per cell
What is unique about Hb production during lifespan?
- alpha globulin produced throughout
- beta globulin produced in 3rd trimester, reaching level 4-6mnths postnatal
What is a haemoglobinopathy?
- inherited condition affecting globin chain synthesis
- autosomal recessive
2 main types of haemoglobinopathies?
- thalassaemia (decreased rate of globin chain synthesis)
- structural haemoglobin variants (normal rate of production, abnormal chain)
Define thalassaemia?
- normal chains
- abnormal production
- alpha thalassemia
- beta thalassemia
Consequences of thalassaemia?
- microcytic hypochromic anaemia
- haemolysis
Explain alpha thalassaemia?
- unaffected individuals have 4 normal genes
- trait = 1 or 2 genes missing = asymptomatic carrier
- HbH disease = only 1 alpha gene left
- Hb Barts hydrops fetalis = no functional genes left
3 degrees of alpha thalassaemia?
- trait
- HbH disease
- Hb Barts hydrops fetalis
Explain beta thalassemia
- point mutation within the gene
- reduced beta production (b+) or absent (b0)
- only seen in adult haemoglobin
- b trait
- b intermedia
- b major
3 degrees of beta thalassemia
- b thalasemia trait
- b thalassemia intermedia
- b thalassaemia major
Explain HbH disease
- only one copy of alpha globulin
- commonest in SE Asia
Symptoms of HbH disease
- only 1 copy of alpha globulin
- jaundice
- splenomegaly
- Anaemias
When does b thalassemia major typically present
- age 6-24mnths
- when HbF drops
management of beta thalassemia major
- regular transfusion
Consequences of an iron overload
- endocrine dysfunction
- cardiac disease
- liver disease
Management of iron overload
- iron chelating drugs (desferrioxamine)
Consequences of ongoing blood transfusion
- iron overload
What causes sickle cell anaemia
- point mutation in codon 6 of the beta globulin
- glutamine substituted to valine
- produces Bs
- HbS causes red cell membrane damage
What is sickle cell trait
- one copy of HbS
- Asymptomatic carrier state
What defines sickle cell anaemia?
- 2 copies of HbS
- distorted cells - block microvascular flow
Precipitants of a sickle crisis
- hypoxia
- dehydration
- stress
Treatment of a sickle cell crisis
- analgesia
- hydration
- oxygen
- antibiotics
- transfusion
Long term management of sickle cell disease?
- prophylactic penicillin
- folic acid supplementation
- hydroxycarbamide
How are haemoglobinopathies diagnosed?
- FBC, Hb, red cell indicies
- blood film
- liquid chromatography
What diagnosises beta thalasemia trait?
- Raised HbA2
