Haemaglobinopathies Flashcards
What are the two globin genes
- Alpha globin gene- Chr 16- zeta 1 and 2 , alpha 1 and 2
- Beta globin genes- Chr 11- 4 genes epsilon, gamma, delta, beta (main one)
What are the constituents of
- normal adult haemoglobin
- Other adult haemoglobin
- Foetal haemoglobin
- Normal adult= HbA - 2 alpha and 2 beta chains
- Other adult= Hb A2 - 2 alpha and 2 delta chains
- Foetal - HbF- 2 alpha and 2 gamma
What is the definition of haemaglobinopathy
- A serious anaemia caused by inheritance of changes in structure/ synthesis of globin chains of the 02 transport protein haemoglobin by both parents
- Autosomal recessive
- Parents are usually healthy carriers
What are the different types of haemaglobinopathies
- Alpha and beta thalassameia
- Haemoglobin E, C ect
- Sickle cell anaemia
- Hbs / B thalassaemia
Thalassaemia occurs in places where malaria is present as people with it have a selective advantage and are protected from malaria
What are the features of alpha thalassaemia
- Genetic defect in one or more of an alpha gloving gene causing failure to produce the globin protein
- Alpha thalassaemia trait- usually symptomless carrier
- Common in south east asia
- Deletion - 1 normal Hb band and 1 abnormal
- If both parents have an alpha trait baby will have Hb parts (death in utero or after birth) or hydros foetalis
What are the features of haemoglobin barts in the foetus
- A failed alpha globin in alpha thalassaemia leads to only 4 gamma globin genes in the foetus = Bart’s -
- if both parents have 2 / 4 defective genes Bart’s can occur (25% chance)- all 4 baby genes are defective
- Foetal haemoglobin has higher o2 affinity so doesn’t give up oxygen easily leading to tissue hypoxia
- There are unstable homotretrameres and inclusion bodies that cause membrane cell damage so that RBCs dont survive
- Haemolysis leads to short RBC survival
- To compensate there is splenomegaly
Discuss the features of HbH disease in alpha thalassaemia
- Failed alpha globin due to alpha thalassaemia
- adult there is combination of 4 beta globin genes - HbH
- 1 parent will have 2/4 defective genes and 1 parent will have 1/4 defective genes
How will alpha thalassaemia show up on blood film and what are the chromosomal defects associated
- Blood film - mild changes on RBC
- Alpha thalassaemia major will show large pale RBC with little to no Hb
- There will be nucleated RBC suggesting increased RBC turnover
-There will be defects on Chr 16 that will cause defective alpha globin genes - thalassaemia trait
Discuss the features of beta thalassaemia
- Major type compatible with life for 1st 6 months- we have foetal Hb - 2 alpha and 2 gamma chains
- Child only becomes anaemic when B chains take over in adult Hb
- Defect in B globin gene causing failure in B globin protein production
- Trait is symptomless unless carrier of B thalassaemia major
What are the features of beta thalassaemia major
- If both parents have the trait then foetus can be beta thalassaemia major- will require life long monthly blood transfusions and nightly iron chelation infusion
- Signs- Small/ prominent head, expanded bone marrow in head, hepatic splenomegaly, transfusions to dampen down haemtopoiesis
- on blood film will have mild anaemia, microcytic and normal MCHC
- Findings- Low Hb, Microcytosis, normal/ Increased reticulocytes, low MCH, normal MCHC
Effect on patient: Microcytic picture but don’t assume iron deficiency- need ferritin measured for iron status
-Screened before pregnancy if carrier
What are the features of sickle cell anaemia
- A single mutation on Beta globin gene at position 6 (changes the 3 letter code) causing amino acids to change from glutamic acid to valine making sickle B globin
- Sickle cell trait- symptomless carrier- West africa, middle east, caribbean
- On blood film: Sickle cell shaped - changed shape due to lack of oxygen, in even mild hypoxia RBCs will undergo conformational change to sickle shape
Treatment: Blood exchanged to have normal Hb
What are the symptoms of sickle cell anaemia
- Yellow conjunctiva/ jaundice due to chronic RBC breakdown
- Splenomegaly due to haemolytic
- Holes in bones/ bone pain
- Thombotic events- repeated cerebral infarcts
