A 12 months old girl of Punjabi parents developed pallor since 3 months of age. One unit of blood transfusion was done at 5 months of age. Now presents with pallor, on examination hepatosplenomegaly. Hemoglobin was 3.8 gm/dl, MCV= 68, MCH = 19. Peripheral smear showed schistocytes. Bone marrow examination show erythroid hyperplasia. Diagnosis is:
Ans. c. Beta-thalassemia (major) (Ref: Robbins 9/e p640, 8/e p649; Ghai 7/e p307; Harrison 19/e p637, 18/e p859)Features in favor of Beta-thalassemia (major):Punjabi parentsPallor since 3 months of ageOne unit of blood transfusion at 5 months of agePresents with pallor and hepatosplenomegalyHb 3.8 gm/dl, MCV= 68, MCH = 19Peripheral smear: SchistocytesBone marrow examination show erythroid hyperplasia.Clinical and Genetic Classification of B-ThalassemiasClinical SyndromesGenotypeClinical FeaturesMolecular Geneticsb-Thalassemia majorHomozygous b- thalassemia (bdeg/bdeg,bdeg+/bdeg+,bdeg/b+)Severe; requires blood transfusionsMainly point mutations that lead to defects in the transcription, splicing, or translation of b-globin mRNAb-ThalassemiaintermediaVariable (bdeg/b+,b+/b+, bdeg/b, b+/b)Severe but does not require regular blood transfusionsb-Thalassemia minorHeterozygous b-thalassemia(bdeg/b,b+/b)Asymptomatic with mild or absent anemia; red cell abnormalities seenb-Thalassemia Majorb-thalassemia major is most common in Mediterranean countries, parts of Africa, and Southeast AsiaQ.Anemia manifests 6 to 9 months after birth as Hb synthesis switches from HbF to HbAQ.In untransfused patients, Hb levels are 3-6 gm/dLQ.The red cells may completely lack HbA (bdeg/bdeg genotype) or contain small amounts (b+/b+ or bdeg/b+ genotypes).Ans. is a.Major red cell hemoglobin is HbF, which is markedly elevatedQ.HbA2 levels are sometimes high but more often are normal or lowQ.Morphology:Blood smears:Marked variation in size (anisocytosis), shape (poikilocytosis), microcytosis, and hypochromiaQ.Target cells, basophilic stippling and fragmented red cellsQInclusions of aggregated alpha chains are efficiently removed by the spleen and not easily seenQ.Reticulocyte count is elevated, but it is lower than expected for the severity of anemia because of the ineffective erythropoiesisQ.Variable numbers of poorly hemoglobinized nucleated red cell precursors (normoblastsQ) are seen in the peripheral blood as a result of "stress" erythropoiesis and abnormal release from sites of extramedullary hematopoiesisQ.In the untransfused patient there is a striking expansion of hematopoietically active marrowQ.In the bones of the face and skull the burgeoning marrow erodes existing cortical bone and induces new bone formation, giving rise to a "crew-cut" appearanceQ on x-ray.Both phagocyte hyperplasia and extramedullary hematopoiesis contribute to enlargement of the spleenQ, which can weigh as much as 1500 gm.Liver and lymph nodes can also be enlarged by extramedullary hematopoiesisQ.Hemosiderosis and secondary hemochromatosis (iron overload) occur in almost all patients.Deposited iron often damages organs, most notably the heart, liver and pancreasQ.Clinical Course:Clinical course of B-thalassemia major is brief unless blood transfusions are givenQ.Untreated children suffer from growth retardation and die at an early ageQ from the effects of anemia.In those who survive long enough, the cheekbones and other bony prominences are enlarged and distortedQ.HepatosplenomegalyQ due to extramedullary hematopoiesis is usually present.Bone marrow transplantation is the only therapy offering a cure and is being used increasinglyQ.Prenatal diagnosis is possible by molecular analysis of DNAQ.
Sickle cell anemia
Alpha-thalassemia
Beta-thalassemia (major)
Glucose-6-phosphate dehydrogenase
Anemia and RBC Disorders