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haemoglobin structure

Normal Haemoglobin. Always 2 Beta-type and 2 Alpha-type globin chains carrying haem moleculeBeta-typeepsilon, gamma, beta, thetaAlpha-typezeta, alpha. Haemoglobin structure. So functional Hb is always a heterotetramerthere must be 2 Beta and 2 Alpha for oxygen carrying functiondifferent types at different stages of fetal and early neonatal lifeby 6 months we have adult proportions.

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haemoglobin structure

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    1. Haemoglobin structure

    2. Normal Haemoglobin Always 2 Beta-type and 2 Alpha-type globin chains carrying haem molecule Beta-type epsilon, gamma, beta, theta Alpha-type zeta, alpha

    4. Haemoglobin structure So functional Hb is always a heterotetramer there must be 2 Beta and 2 Alpha for oxygen carrying function different types at different stages of fetal and early neonatal life by 6 months we have adult proportions

    5. Hb development Up to 8/40 zeta2/epsilon2, alpha2/epsilon2, zeta2/gamma2 From 8/40 to birth 85% alpha2/gamma2 (HbF) 5-10% alpha2/beta2 (HbA) remainder alpha2/theta2 (HbA2) + others By 6/12, adult proportions of A, A2, F

    6. Normal adult Hb HbA (alpha2/beta2) 97% + HbA2 (alpha2/theta2) 2-3% HbF (alpha2/gamma2) 0.5% or less NOTE ALL NEED ALPHA!

    7. Haemoglobin abnormalities Haemoglobinopathies normal amounts of abnormal beta chains crystalline disorders (S, C, D, E) familial polycythaemia, M Hb, unstable Hb, HPFH Thalassaemias reduced amounts of normal alpha or beta chains Can be BOTH!

    8. Thalassaemias (simplistic) Reduced production of BETA chains BETA thalassaemias Reduced production of ALPHA chains ALPHA thalassaemias more severe clinical disease

    9. Beta thalassaemias Beta chain deficiency So reduced HbA BUT retained production of other beta-type chains, so increased theta production (HbA2) gamma production (HbF)

    10. Beta thalassaemias Encoded by a single gene pair Autosomal recessive (but not totally) heterozygotes have beta thalassaemia trait homozygotes have beta thalassaemia (thalassaemia MAJOR) but they are ALIVE at birth variable clinical severity - why?

    11. Inheritance of beta thalassaemia

    12. Beta plus thalassaemia genes If the mutation causes total shutdown of the beta chain gene no beta chain produced Beta nought thalassaemia If the mutation reduces beta chain production (but does not shut it down) some beta chain produced Beta plus thalassaemia

    13. Combinations Beta/beta plus heterozygote microcytosis, Hb normal raised A2 and F Beta/beta nought heterozygote more severe microcytosis, Hb normal raised A2 and F

    14. Combinations Beta plus/beta plus microcytosis, +/- anaemia Beta nought/beta nought microcytosis, red cell changes, transfusion dependent Beta plus/beta nought microcytosis, variably anaemic

    15. Inheritance of alpha thalassaemia More complex as encoded by 2 gene pairs (so four genes per person, not two) However, usually due to whole gene deletions, so total gene loss/shutdown haematology and clinical presentation depends on how many genes are lost

    16. Gene deletions in alpha thalassaemia

    17. Gene deletions in alpha thalassaemia

    18. Gene deletions in alpha thalassaemia

    19. Clinical disorders Alpha/alpha + alpha thalassaemia trait, normal Hb, normal or slightly reduced MCV Alpha +/Alpha + or alpha/alpha 0 normal Hb, microcytic

    20. Clinical disorders Alpha +/alpha 0 HbH disease, reduced Hb, splenomegaly, may or may not be transfusion dependent presence of beta tetramers (HbH) on film (“golf ball” cells) unlike in beta thalassaemia, there is no substitute for alpha

    21. Hydrops fetalis Four gene deletion no alpha chain production incompatible with life fetus dies in utero gamma tetramers instead - Hb Barts

    22. HbH and Hb Barts

    23. Laboratory diagnosis Beta thalassaemia relies on raised F and A2 Alpha thalassaemia F and A2 normal may see “golf balls” on HbH prep gene analysis

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