THALASSEMIA

Definition:

Thalassaemia is an inherited autosomal recessive blood disease. In which the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of theα- or β- globin chains of Hb ,resulting in defected Hb & secondary RBCs defects.

A disease characterized by unbalance in the Hb synthesis, as there is underproduction /no production of one globin chain .Unmatched globin precipitate , damaging RBCs membranes, causing there haemolysis while still in marrow.

Types Of ThalassemiaBasis Of Classification :

1-Gene deletion/α -Thalassemia.

2-gene mutation/β-Thalassemia.

α-Thalassemia subtypes.Clinical nomenclature

Genotype Disease Molecular basis Of disease

Silent carrier -α/αα Normal RBCs , asymptomatic patient .

Deletion of one gene .

α-Thalassemia trait -/αα (Asian), -α/-α(black African)

Asymtomatic carrier, ↓MCV

Deletion of two genes.

HbH disease - -/-α Moderately sever anemia , features of haemolysis , hepato- spleenomegaly, leg ulcers & jaundice.

Deletion of three genes.

Hydrops fetalis -/- Death in utero Deletion of all the four genes.

β-Thalassemia subtypes

Clinical nomenclature

Genotype Disease Molecular basis of disease.

β-Thalassemia minor /trait

heterozygous state.(β7/β⁺)

Carrier but asymptomatic,mild microctic anemia, microcytic without anemia, MCV<75fL,

Point mutation.

β-thalassemia intermedia

HomozygousState(β⁺/β⁺)

Moderate anemia no transfusion ,spleeno megaly ,

Point mutation.

β-thalassemia major

Homozygous/compound heterozygous (β⁺/β⁺,β77/β7,7β⁺/β7)

Sever anemia ,facial deformities,Hepatospleenomegaly

Point mutation.