Question

What is gene therapy ? Can it be used for treatment of sickle -cell anaemia, haemophilia and thalassemia?

Answer 1

In this disorder beta chain production is reduced or totally absent.Excess alpha chains precipitate and cause haemolysis and there is increased production of Hb F and Hb A2. Unlike alpha thalassemia defects are mainly point mutations rather than gene defects.Types of beta thalassemia 1) Thalassemia major 2) Thalassemia intermedia3) Thalassemia major Clinical syndromes 1)Thalassemia minorAsymptomatic carrier state.Mild microcytic hypochromic anemia and often confused with irondeficiency anemia. But iron studies are normal.Hb electrophoresis show raised Hb A2 and mild increased in Hb F.2) Thalassemia intermediaSymptomatic with moderate anemia but do not require regular transfusionSpleenomegaly is present along with bony deformities, leg ulcers, gall stones, and infection.2)Thalassemia major (Cooley’s anemia)Present in the first year withFailure to thrive Severe anemia after 3-6 monthsExtramedullary haemopoiesis causing hepatosplenomegaly and bone marrow expansion. They have classical thalassemia facies called chipmunk facies.X ray skull show hair on endappearance(due to cortical bone expansion)Hb electrophoresis show increased Hb F and markedly reduced Hb A.Treatment Aim is to suppress the ineffective erythropoeisis.

Folic acid supplements and blood transfusion to keep the Hb >10gm%.If transfusion is required in increased amounts spleenectomy is required. (Same precautions to be taken as mentioned before).Iron over load due repeated transfusion is major problem. This can be treated with iron chelating agent desferrioaxamine.but it can be given only in parental route and anaphylaxis is also common.Ascorbic acid to increased excretion of iron can also be given.Bone marrow transplantation in young patients with HLA matched donorshave good success rate.