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Stem
A 9-month-old boy of Gujarati origin is brought by his parents with progressive pallor, poor feeding and failure to thrive for two months. On examination he is pale and icteric, with frontal bossing, maxillary prominence, and a palpable spleen 6 cm below the costal margin and liver 4 cm.
Investigations: Hb 54 g/L, MCV 58 fL, MCH 18 pg, RBC count 4.2 (low-normal for the anaemia), reticulocytes 6 percent. Peripheral film: marked microcytic hypochromic anaemia with target cells, basophilic stippling and nucleated red cells. Serum ferritin is normal. Hb electrophoresis (HPLC): HbF 85 percent, HbA2 5 percent, HbA absent.
Questions
a) What is the diagnosis and which two findings in the stem and investigations support it? (2 marks)
b) Explain the pathophysiology of the frontal bossing and hepatosplenomegaly. (2 marks)
c) Outline the management of this child. (4 marks)
d) What is the leading cause of death in this condition, how is it monitored, and how is it prevented? (2 marks)
Model answers
a) Beta-thalassaemia major (Cooley anaemia). Supporting features: (i) presentation in infancy — GeneReviews six to 24 months; Muncie second six months of life — with severe microcytic hypochromic anaemia, failure to thrive, frontal bossing and hepatosplenomegaly; (ii) electrophoresis showing raised HbF with absent HbA (GeneReviews table: HbF up to 95%, HbA typically near 0%) and raised HbA2.
b) Unbalanced globin synthesis causes ineffective erythropoiesis, increased haemolysis and deranged iron homoeostasis (Kattamis). Marrow expansion produces the bony facies (frontal bossing, maxillary overgrowth). Extramedullary haematopoiesis plus splenic clearance of damaged red cells causes hepatosplenomegaly.
c) (1) Regular lifelong transfusion — Muncie: keep haemoglobin higher than 9.5 g/dL (95 g/L) to sustain normal growth; GeneReviews: 9.5–10.5 g/dL; DEEP-2 defined transfusion dependence as at least 150 mL/kg/year of red cells. (2) Iron chelation is mandatory once iron accumulates (Muncie); DEEP-2 doses deferiprone 75–100 or deferasirox 20–40 mg/kg/day; EPIC starts deferasirox at 20 mg/kg/day on 2–4 units/month. (3) Folate as supportive care (GeneReviews, intermedia/major adjuncts). (4) Splenectomy only for hypersplenism (Kumar); Muncie delays surgery until at least four years and vaccinates at least one month beforehand. (5) Cardiac MRI T2-star surveillance (Pennell: T2* <10 ms predicts heart failure). (6) Curative option: allogeneic HSCT if a matched sibling is available (Kattamis; GeneReviews DFS greater than 90% in low-risk children); gene therapy beti-cel produced TI in 20/22 (91%) evaluable non-β0/β0 patients (Locatelli).
d) Heart failure from cardiac iron is the most common cause of death (Pennell). Monitor with cardiac MRI T2-star — ferritin and liver iron are not adequate surrogates — and prevent with lifelong chelation. Muncie: untreated cardiac iron often kills by 30 years of age.