A mother brings her 2 year old son to a pediatrician.

She just recently observes that her son looks pale. She also just realized that her son is smaller than his peer. His elder sister, 4 years old is completely healthy without such complaints. After taking clinical history and physical examination, the doctor decide to proceed with additional examinations. Blood examination reveals severe anemia with decreased MCV abd MCH. On peripheral blood smear, there are marked anisocytosis and poikilocytosis with many nucleated red cells, contracted red cells and polychromasia. Hemoglobin electrophoresis shows marked increase of HbF and elevated HbA2. The doctor diagnoses him as having beta thalassemia major.

Further DNA analysis revealed the presence of 2 mutations in the globin gene of the patient, including single nucleotide substitution in codon 26 (GAG -> AAG) and mutation in intron 1 (IVS1 - 5G>C). His father carries the heterozygote mutation in codon 26, while his mother has heterozygote mutation in intron 1. Based on those data, the doctor established a final diagnosis of beta thalassemia compound heterozygote for the boy.