A 9-month-old infant girl presents to the emergency department with her concerned parent. She has seemed tired and fussier than normal over the past 3 months, and the mother thinks she is starting to develop abnormal physical features, most noticeably a large head. Her mother reports that her pediatrician ordered lab tests recently which showed a low red blood cell count. The infant was fine until 6 months old and was meeting all her developmental milestones. She is up to date with vaccinations. Family medical history is unremarkable. She is mildly tachypneic with normal oxygen saturation. The rest of her vital signs are within normal limits. On physical examination, the infant is noted to have slight pallor. She has frontal bossing, a depressed nasal bridge, and is short for her age. A complete blood count shows severe microcytic anemia. Further tests are ordered to confirm the suspected diagnosis.
Which of the following results would be expected regarding the most likely diagnosis?
B) Hemoglobin electrophoresis showing elevated alpha hemoglobin protein
The suspected diagnosis is beta-thalassemia, given the age of onset (between 6 and 24 months, after fetal hemoglobin switches to alpha hemoglobin), skeletal abnormalities (caused by extra-medullary RBC production), family history (signs of a genetic predisposition to anemia), and signs and tests identifying anemia with microcytosis. Beta-thalassemia is caused by genetic variants in the HBB gene, leading to reduced production of the beta-hemoglobin chain and thus an increase in the alpha-chain is seen on hemoglobin electrophoresis. If both copies of the gene have mutations, it causes beta-thalassemia major, and patients often become transfusion dependent.
The differential diagnosis for microcytic anemia should include iron deficiency, sideroblastic anemia, anemia of chronic disease (unlikely in this case), beta-thalassemia, and lead poisoning.
Answer choice A: Basophilic stippling on blood smear, is incorrect. Basophilic stippling may be seen in beta-thalassemia but is also present in lead poisoning and thus does not differentiate the cause of a microcytic anemia enough.
Answer choice C: Hypochromic red blood cells with erythroblasts on blood smear, is incorrect. Hypochromia is a very non-specific sign, seen in other conditions such as vitamin B6 deficiency or chronic bleeding. Erythroblasts are immature red blood cells which are often present in cases of severe anemia.
Answer choice D: Low serum ferrtin, is incorrect. Low serum ferritin is seen in iron deficiency anemia.
Answer choice E: Mean corpuscular volume to red blood cell count ratio (MCV: RBC) > 13, is incorrect. This represents the Mentzer index, which helps differentiate iron deficiency anemia from beta-thalassemia in children. A ratio > 13 indicates iron deficiency, whereas a ratio <13 indicates beta-thalassemia.
Key Learning Point
Beta-thalassemia is caused by genetic variants in the HBB gene, leading to reduced production of the beta-hemoglobin chain and thus an increase in the alpha-chain is seen on hemoglobin electrophoresis.
