A range of disorders arising from imbalanced globin production The Thalassaemias A range of disorders arising from imbalanced globin production

The Thalassaemias To recap And these chains are all “normal” Haemoglobin A has two a and two b chains (>95% of total Hb) Haemoglobin A2 has two a and two d chains (2-3% of total Hb) Haemoglobin F has two a and two g chains (<1% of total Hb) And these chains are all “normal”

The Thalassaemias and you’ve got one beta globin gene on chromosome 11 each cell has two chromosomes 11 a total of two beta globin genes exist in each cell. two alpha globin genes on chromosome 16 each cell has two chromosomes 16 a total of four alpha globin genes exist in each cell.

The Beta Thalassaemias Major Two malfunctioning/absent genes No production of beta chains surplus production of alpha chains which precipitate on cell membranes haemolysis & inefficient haemopoesis haemopoetic hyperplasia Minor One malfunctioning/absent gene reduced production of beta chains surplus production of alpha chains which is compensated well by the body Hb A2 a2d2

The Beta Thalassaemias Intermedia Midway in severity between minor and major reduced production of beta chains surplus production of alpha chains which is compensated well by the body One or two malfunctioning genes ?!?!?!?! Hb A2 a2d2

The Beta Thalassaemias Population β-gene Mutation Severity Indian -619 del βο Mediterranean -101 β++ African -88 Mediterranean; African -87 Japanese -31 -29 Southeast Asian -28 Mediterranean; Asian Indian IVS1-nt1 IVS1-nt5 Βο ΙΩΣ1-nt6 β+/++ IVS1-nt110 β+ Chinese IVS2-nt654 IVS2-nt745 codon 39 codon 5 Mediterranean; African-American codon 6 codons 41/42 African-American AATAAA to AACAAA

The Beta Thalassaemias Normal beta genes Either absent or on a “go-slow” Hb Barts g4 Raised Hb A2

The Alpha Thalassaemias To recap Haemoglobin A has two a and two b chains (>95% of total Hb) Haemoglobin A2 has two a and two d chains (2-3% of total Hb) Haemoglobin F has two a and two g chains (<1% of total Hb) And these chains are all “normal” two alpha globin genes on chromosome 16 each cell has two chromosomes 16 a total of four alpha globin genes exist in each cell.

Hydrops fetalis (major) The Alpha Thalassaemias a globin problems are often clinically silent one “duff” gene has three backups Genotype α Genes Description αα/αα 4 Normal αα/α- 3 Silent carrier --/αα or α-/α- 2 Thal minor/trait --/α- 1 Hgb H disease --/-- Hydrops fetalis (major)

The Alpha Thalassaemias In the absence of a chains, the b and g chains can form tetramers Hb H b4 Hb Barts g4