Important presentation about Thalassemia (Microcytic Anemia)

• Definition: hereditary underproduction of either the alpha or beta globin chains of the hemoglobin A  resulting in a  microcytic anemia.
• Beta thalassemias are due to mutations in the HBB gene on chromosome 11.
• The α thalassemias involve the genes HBA1 and HBA2 on chromosome 16.

Beta- Thalassemia

• The β-globin mutations associated with β-thalassemia fall into two categories: 
• (1) β0, in which no β-globin chains are produced; and 
• (2) β+, in which there is reduced (but detectable) β-globin synthesis
• Individuals inheriting one abnormal allele have thalassemia minor or thalassemia trait, which is asymptomatic or mildly symptomatic. 
• Most individuals inheriting any two β0 and β+ alleles have β-thalassemia major; 
• occasionally, individuals inheriting two β+ alleles have a milder disease termed β-thalassemia intermedia.

Alpha-Thalassemias

• alpha- thalassemias result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns.The excess β chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains) which have abnormal . The severity of the alpha- thalassemias is correlated with the number of affected alpha-globin genes.  
•  alpha0 thalassaemias, where there is lots of gama4 but no alpha-globins at all (referred to as Hb Barts), often result in still birth.

• The most severe form of alpha thalassemia major causes stillbirth.
• Other symptoms can include:
• Bone deformities in the face
• Fatigue
• Growth failure
• Shortness of breath
• splenomegaly

Diagnostic features of beta-thalassaemia

Dx

• A physical exam may reveal a swollen (enlarged) spleen.
• Blood test:
• Red blood cells will appear small and abnormally shaped when looked at under a microscope.
• A complete blood count (CBC) reveals anemia.
• A test called hemoglobin electrophoresis shows the presence of an abnormal form of hemoglobin

Rx

• Treatment for thalassemia major often involves regular blood transfusions and folate supplements.
• If you receive blood transfusions, you should not take iron supplements. Doing so can cause a high amount of iron to build up in the body, which can be harmful.
• Persons who receive significant numbers of blood transfusions need a treatment called chelation therapy to remove excess iron from the body.
• Bone marrow transplant may help treat the disease in some patients, especially children.
• Hydrops fetalis: none available 
• Haemoglobin H: no specific therapy required; avoid iron therapy; folic acid if necessary 

TREATMENT OF BETA-THALASSAEMIA MAJOR