Thalassemia

Beta thal

• hetergenous disease


• Mutations - B+ (decreased pdc), B0 (no pdc).


• Phenotype is variable - unidentified modifying genes


• Beta-minor - B/B+ or B/B0, usually asymptomatic, microcytic (MCV<>
• Beta-intermedia -symptomatic thal but able to survive to the 2nd decade with no chronic transfusion therapy
• Beta-major - B0/B0 or B+/B+
• Diagnosis — The diagnosis of beta thalassemia minor or intermedia should be entertained in patients of any age with microcytic, hypochromic red cells. the beta thalassemias show considerable heterogeneity, patients may or may not have symptoms referable to anemia, may have variable degrees of splenomegaly and variable degrees of hemolysis.

The major differential diagnosis in such patients includes iron deficiency and the anemia of chronic inflammation, as follows:

• Patients with iron deficiency will have low levels of serum iron and ferritin and increased levels of transferrin (total iron binding capacity). A cause for blood loss will be obvious in most patients.
• Patients with the anemia of chronic inflammation will have low levels of serum iron and transferrin. Levels of ferritin will be normal or increased. An inflammatory, infectious, or malignant disease is usually the underlying cause.
• Patients with thalassemia will have normal to increased levels of serum iron and ferritin. Levels of transferrin will be normal or decreased. At least one of the patient's parents will also be affected. A family history of "iron deficiency anemia" not responding to treatment with iron is common.

The diagnosis of a beta thalassemic condition is confirmed on hemoglobin electrophoresis (table 1 and table 3). Hemoglobin A will be the major hemoglobin present. Levels of hemoglobin A2 are increased in virtually all patients, while levels of hemoglobin F are increased in about 50 percent of patients.

If hemoglobin S is present on electrophoresis along with hypochromic, microcytic red cells, and iron deficiency is absent, one of the sickle cell/thalassemia conditions is present.

• Hb A - 2 alpha, 2 beta
• Hb A2 - 2 alpha, 2 delta
• Hb F - 2 alpha and 2 gamma

Alpha thal

• 4 functional genes. two on each chromosome
• Loss of 1 - alpha thal, silent carrier.
• Loss of 2 - alpha thal minor
• Loss of 3 - alpha thal major, hemoglobin H disease. moderate degree of anemia, their red cells are microcytic, and their hemoglobin electrophoresis pattern shows 5 to 30 percent hemoglobin H (beta-4 tetramers). Chronic hemolytic anemia.
  
• Loss of 4 - hydrops fetalis

Diagnosis —

• The peripheral blood film in Hb H disease shows hypochromia and microcytosis ( readily detectable inclusion .
• Bone marrow examination reveals erythroid hyperplasia with poorly hemoglobinized erythroblasts carrying inclusion bodies.
• The diagnosis of hemoglobin H disease is confirmed by finding Hb H in circulating red cells, in concentrations from 5 to 30 percent, using a number of hemoglobin electrophoretic or chromatographic techniques (table 1 and figure 1). In addition, Hb Barts (gamma-4), a fast-moving hemoglobin, can be detected in concentrations of about 20 to 40 percent at the time of birth of a child with hemoglobin H disease [55]. This latter test has been successfully employed in California as a screening test for hemoglobin H disease [61].
• DNA-based genotyping is required for precise diagnosis, and is especially important in prenatal testing and genetic counseling (see 'Genetic counseling and antenatal diagnosis' below).