Review Question - QID 107262

An asymptomatic patient of Mediterranean origin presenting with isolated, microcytic anemia is most likely due to beta thalassemia minor. This patient would present with increased levels of hemoglobin A2 on gel electrophoresis.

Alpha and beta thalassemias are hemoglobinopathies that are typically due to defect in the alpha and beta globin genes, respectively. Imbalances of globin chain synthesis in both causes can cause hemolysis and impair erythropoiesis requiring lifelong blood transfusions in cases where more than 2 out of the 4 alpha genes are affected, or both beta genes are affected. This typically leads to complications over the long term, with most patients with beta thalassemia dying from cardiac complications from iron overload. Chelation therapy is often necessary to remove iron, with bone marrow transplant being curative in some cases.

Munchie et al. discuss alpha and beta thalassemia. They state that alpha thalassemia occurs most often in persons of African and Southeast Asian descent, and beta thalassemia occurs most often in persons of Mediterranean, African, and Southeast Asian descent. They also state that thalassemia traits affects 5 to 30 percent of persons in these ethnic groups. Alpha thalassemia typically results from impaired production of the alpha globin genes (four total) on chromosome 16 while the beta counterpart results from a similar situation of beta genes on chromosome 11. Gel electrophoreses for beta thalassemia normally shows increased amount of hemoglobin A2. Hemoglobin A2 (two alpha and two delta globin chains) is normally a minor component of total hemoglobin, with hemoglobin A (two alpha and two beta globin chains), but in patients with beta thalassemia (both minor and major), decreased beta globin production usually results in increased amounts of hemoglobin A2. Fetal hemoglobin (hemoglobin F) is also typically increased in beta thalassemia trait and is the dominant hemoglobin in beta thalassemia major.

Sherief et al. report on nutrition in children suffering from beta thalassemia. In their retrospective study, they report that there was a significant decrease of vitamins A, C, E, and B12 and trace elements zinc, copper, and selenium in thalassemic patients compared to their matched controls. They also report that total homocysteine and methylmalonic acid levels were significantly elevated in patients due to vitamin deficiencies and recommend more frequent nutritional testing in patients suffering from thalassemias.

Figure A shows microcytic red blood cells along with target cells and teardrop cells.

Incorrect Answers:
Answer 1 and 2: Alpha thalassemias would present with increased levels of beta globin chains and gamma globin chains. In disorders where 3 or 4 of the alpha chains were affected, there would be an increase in Hemoglobin H and Hemoglobin Bart's corresponding to above chains, respectively.
Answer 4: Beta thalassemia major affects both of the globin genes and would normally present with jaundice, pallor, skeletal abnormalities, splenomegaly. It would also require lifelong blood transfusions and is less likely in this asymptomatic patients.
Answer 5: The patient has normal iron studies so it is unlikely he has iron deficiency anemia.