Posts: 3,675,937
Threads: 734,344
Joined:
Sep 2021
Reputation:
5
A 25-year-old asymptomatic African American woman has had a mild microcytic anemia since early childhood. She has a normal menstrual history. Physical examination is normal. Laboratory studies show a mild microcytic anemia and decreased hemoglobin (Hb) and hematocrit (Hct); however, the red blood cell count (RBC) is increased. The hemoglobin electrophoresis is normal. Serum ferritin is normal. Which of the following is the most likely diagnosis?
A. Iron deficiency
B. Sickle cell trait
C. Sideroblastic anemia
D. α-Thalassemia
E. β-Thalassemia
Posts: 3,675,937
Threads: 734,344
Joined:
Sep 2021
Reputation:
5
It will be too easy ....try again
Posts: 3,675,937
Threads: 734,344
Joined:
Sep 2021
Reputation:
5
This one is unusual ...
Option D (alpha-Thalassemia) is correct. alpha-Thalassemia is an autosomal recessive disorder that involves decreased production of gamma globin chains. Gamma globin chain synthesis is controlled by four genes. Delection of two of these genes causes a mild microcytic anemia with decreased synthesis of hemoglobin A (2α2β), hemoglobin A2 (2α2δ), and hemoglobin F (2α2γ). For unexplained reasons, the RBC count is increased in all the thalassemias, while it is decreased in all the other microcytic anemias (e.g., iron deficiency anemia). Hemoglobin electrophoresis is normal because the proportion of each of the hemoglobins remains the same even though there is a decrease in the Hb concentration. Recall that all the normal hemoglobins require gamma globin chains. Because alpha -thalassemia involves the synthesis of globin chains rather than the synthesis of heme, which requires iron, the serum ferritin level is normal as are all the other iron studies (e.g., serum iron, total iron binding capacity). There is no treatment.
The clinical course of β-thalassemia major is brief unless blood transfusions are given. Untreated children suffer from growth retardation and die at an early age from the profound effects of anemia. Blood transfusions not only improve the anemia but also suppress secondary features related to excessive erythropoiesis. In those who survive long enough, the cheekbones and other bony prominences are enlarged and distorted. Hepatosplenomegaly due to extramedullary hematopoiesis is usually present. Cardiac disease resulting from progressive iron overload and secondary hemochromatosis (Chapter 18) is an important cause of death, particularly in heavily transfused patients. Administration of iron chelators can forestall or prevent this complication. With transfusions and iron chelation, survival into the third decade is possible, but the overall outlook remains guarded. Bone marrow transplantation from an HLA-identical sibling is currently the only therapy offering a cure. Prenatal diagnosis is possible by molecular analysis of DNA.
Thalassemia Minor. Thalassemia minor is much more common than thalassemia major and understandably affects the same ethnic groups. Most patients are heterozygous carriers of a β+ or β0 gene. Thalassemia trait may offer resistance against falciparum malaria, accounting for its prevalence in parts of the world where malaria is endemic. These patients are usually asymptomatic, and anemia is mild if present. The peripheral blood smear typically shows some red cell abnormalities, including hypochromia, microcytosis, basophilic stippling, and target cells. Mild erythroid hyperplasia is seen in the bone marrow. Hemoglobin electrophoresis characteristically reveals an increase in HbA2 to 4% to 8% of the total hemoglobin (normal, 2.5% ± 0.3%). HbF levels can be normal or slightly increased. Recognition of β-thalassemia trait is important on two counts: (1) differentiation from the hypochromic microcytic anemia of iron deficiency and (2) genetic counseling. Iron deficiency can usually be excluded as the cause of a microcytic anemia through measurement of serum iron, total iron-binding capacity, and serum ferritin (see Iron Deficiency Anemia). Hemoglobin electrophoresis is a very helpful confirmatory test for β-thalassemia trait, particularly in individuals (such as women of childbearing age) at risk for both thalassemia trait and iron deficiency.
