Haemoglobinopathies
Objectives:
Understand the molecular pathophysiology of a mendelian genetic disease- using haemoglobinopathies as examples describe how differences in mutations mat affect disease phenotype and treatment outline prevention and treatment strategies for beta thalassemia
Haemoglobinopathies
- alpha thalassemia
- beta thalassemia
Haemoglobin
for haemoglobin you need iron + poryphorin = haem haem + globin(alpha + beta) = haemoglobin
Haemoglobinopathies are rather common the big 2 are sickle cell thalassemia can be”
- major
- intermedia
- minor (better named trait than a disorder)
Genetic basis of thalassemia
you need at least 2 copies of a globin 1 copy of b globin
if alpha is knocked out then it disrupts all types and you see beta and gamma tetramers
if beta is knocked out you see mainly gamma and delta normal units
Fetal haemoglobin
there is a shift in globin production from fetal to infant stages
onset of beta symptoms occur around 3 months after birth due to beta replacing gamma alpha replacement occurs in utero
Thalassemia may confer improved immunity to malaria minor or trait are carriers
b trait/ carriers are highly present in the Mediterranean
allelic hetergeneity
many different mutated alleles responsible for thalassemia depending where you go in the world locus heterogeneity modifier genes
Prevention of Thalassemia
mild anaemia form 2 a globin copies
Different therapies to treat a disorder based on different interventions in the central dogma casgevy crispr to ensure gamma and delta haemoglobin continue being produced public health approaches to preventing b thalassemia includes prevention of birth
Treatment of Thalassemia