Haemoglobinopathies Flashcards
what are Haemoglobinopathies
commonest monogenic disorders worldwide
disorders caused by pathogenic sequence variants in the genes that direct synthesis of the globin chains of Haemoglobin (Hb).
what is alpha thalassemia
the most widely distributed of all globin disorders
caused by a deficit in α globin chain production.
four loci of alpha-globin (2 on each Chr 16: HBA1 and HBA2.).
Deletion of one (- α) or both (- -) α-genes is the most frequent cause of α-thalassemia (~90 %), however point mutations in α2 (α+α) or α1 (αα+) also occur (~10 %).
what are the 2 symptomatic forms of alpha thalassemia
One deletion: Silent Carrier
Two deletions: Alpha-thalassemia Minor
describe HbH Disease
Three alpha-globin deletions: shortage of alpha-globin.
cells produce an abnormal form of haemoglobin called haemoglobin H (HbH) consisting of β4 tetramers. abnormal haemoglobin cannot effectively carry oxygen to the body’s tissues.
Most patients survive to adult life and only become transfusion-dependent in their later years. compound heterozygotes or homozygotes
describe Hb Barts Hydrops Fetalis Syndrome.
Deletion of all four alpha-globin chains
severest form of α-thal) and is incompatible with post natal life
describe Alpha-thalassemia retardation-16 (ATR-16) syndrome
16p del encompassing HBA1 and HBA2.
microcephaly, short stature: variable; low IQ. distinctive Facial features; talipes, hypospadias and cryptorchidism in males
what is Beta thalassemia
reduced or absent beta globin chain synthesis which in turn results in reduced Hb in RBCs, decreased RBC production and anaemia.
11p: contains the beta globin gene, delta globin gene, the embryonic epsilon gene, the fetal A-gamma and G-gamma genes, and a pseudogene (ψB1).
discuss mutations in Beta thalassemia
heterogeneous at the molecular level; >280 mutations: single nucleotide substitutions, deletions, insertions or frameshift mutations. Gross gene deletions are rare
describe Beta-thalassaemia major
(the most severe form of thalassaemia)
severe anaemia and hepatosplenomegaly.
affects infants from approx 6 months of age. They are transfusion dependent within 2 years of life.
describe Beta-thalassemia intermedia
present later than beta-thalassemia major and present usually with mild anaemia. need occasional transfusions
what is Sickle cell disease (SCD)
autosomal recessive disorder which shows overdominance (heterozygote advantage).
RBCs: abnormal rigid sickle shape when viewed microscopically caused by point mutations in HBB.
conditions of low Oxygen (hypoxia), acidity and cellular dehydration polymerisation of HbS within red blood cells leads to their deformation into the sickle shape.
Describe Sickle cell anaemia
p.Glu6Val mutation in HBB, known as HbS.
Affected individuals are homozygous for this mutation (HbSS
discuss NHS Sickle Cell & Thalassaemia Screening Programme
Newborn screening
Antenatal screening:
All women in England are offered screening by 10+0 week
If a woman is identified as a carrier, the baby’s father is also offered screening.
