Paper I
Question
A seven-year-old boy presented to the hospital with breathlessness and severe pallor. On examination he had stunted growth, frontal bossing, mild icterus and moderate splenomegaly. History of repeated blood transfusions was present. Investigations revealed Hb- 3gm%, TLC – 5600/cu.mm, platelets – 3.0 lakhs/cu.mm. Peripheral smear showed microcytic hypochromic blood picture with marked anisopoikilocytosis, many target cells and reticulocyte count of 5%. (
- (a) What is the likely diagnosis and why ( 2 mark(s)
- (b) What is the pathogenesis of this condition ( 4 mark(s)
- (c) What are the laboratory investigations needed in such a case to diagnose the disease and the expected results ( 6 mark(s)
- (d) How do you classify this disease based on its clinicohematological profile. 3 mark(s)
Answer
(a) Likely diagnosis and why
- Beta-thalassaemia major (Cooley’s anaemia)
- Supporting features: young child with severe transfusion-dependent anaemia (Hb 3 g%), stunted growth, frontal bossing (marrow expansion from ineffective erythropoiesis), icterus (haemolysis), splenomegaly (extramedullary haematopoiesis and destruction of abnormal red cells), microcytic hypochromic picture with marked anisopoikilocytosis, numerous target cells, and reticulocytosis — a classic clinicohaematological picture of a severe inherited haemolytic anaemia with ineffective erythropoiesis
(b) Pathogenesis
- Mutation in the beta-globin gene leads to absent or markedly reduced beta-globin chain synthesis
- Unpaired excess alpha-globin chains precipitate within red cell precursors, causing membrane damage and premature destruction of erythroid precursors within the bone marrow (ineffective erythropoiesis) and shortened survival of mature red cells in the periphery (haemolysis)
- Ineffective erythropoiesis stimulates massive compensatory marrow expansion, causing skeletal deformities (frontal bossing, “hair-on-end” appearance on skull X-ray, maxillary hyperplasia)
- Chronic haemolysis and repeated transfusions lead to iron overload, causing secondary haemochromatosis affecting the heart, liver, and endocrine organs
(c) Laboratory investigations and expected results
- Complete blood count: Severe microcytic hypochromic anaemia, low MCV/MCH
- Peripheral smear: Marked anisopoikilocytosis, target cells, microcytes, nucleated red blood cells, basophilic stippling
- Reticulocyte count: Elevated (compensatory, though blunted relative to the degree of anaemia due to ineffective erythropoiesis)
- Haemoglobin electrophoresis / HPLC: Absent or markedly reduced HbA, markedly elevated HbF, variable HbA2 — the definitive diagnostic test
- Serum iron studies: Elevated serum ferritin/iron, low TIBC (iron overload from haemolysis and transfusions)
- Skull X-ray: “Hair-on-end” appearance due to marrow expansion
- Family studies/genetic testing: Beta-globin gene mutation analysis; parents typically show thalassaemia trait (minor)
(d) Classification based on clinicohaematological profile
- Thalassaemia minor (trait): Heterozygous, mild/asymptomatic microcytic anaemia
- Thalassaemia intermedia: Moderate anaemia, not usually transfusion-dependent
- Thalassaemia major: Homozygous/compound heterozygous, severe transfusion-dependent anaemia presenting in infancy/early childhood (as in this case)