A 12-year-old boy born to a couple, originally from Greece visited the Emergency Department because of abdominal and bilateral lower extremity pain. His history indicated that he had anemia and had been receiving red cell transfusion intermittently from a very young age. He was admitted to the hospital 5 times in the last two years with the same diagnosis, and the usual sites of pain included the abdomen and bilateral extremities. The boy seemed in acute distress with jaundice noted and tendered on his extremities’ palpation on physical examination. No other remarkable abnormalities were present.
A full blood count showed the following results. Blood film observation was performed and a representative field was shown as below. Peripheral blood (May-Grunwald-Giemsa (MGG) staining, ×500). Haemoglobin electrophoresis showed 88% HbS, 10% HbF (normal range 0-2%), and 2% HbA2 (normal range 0-3.5%).
- Which morphological abnormalities are present in the blood smear? What is the significance of the presence of the arrowed cells and the cell with a nucleus in the peripheral blood? (2 marks) (Maximum 100 words)
- What is the most likely diagnosis? Discuss the inheritance pattern of this disorder. Is this patient heterozygous or homozygous for the disorder? What is the cause of this patient’s pain? (4 marks) (Maximum 200 words)
- What is the molecular basis of this disorder? Please also include how the arrowed cells are formed in your answers. (2 marks) (Maximum 100 words)
- Which other laboratory tests may be required to further support the diagnosis? Which results you would expect to be obtained? (2 marks) (Maximum 100 words)