An 8-year-old boy has hypochromic microcytic anaemia refractory to oral iron. Peripheral smear shows dimorphic red cells, and bone marrow reveals ringed sideroblasts. His maternal uncle had a similar untreated anaemia. The underlying defect involves:

• A Defective globin chain synthesis with excess alpha chains
• B Deficiency of uroporphyrinogen III synthase in marrow precursors
• C Autoimmune destruction of gastric parietal cells
• D Mutation of the erythroid-specific ALA synthase gene (ALAS2) ✓

Explanation

X-linked sideroblastic anaemia arises from mutations in ALAS2, the erythroid-specific isoform of delta-ALA synthase, impairing the first committed step of heme synthesis. Iron enters mitochondria but cannot be incorporated, producing perinuclear mitochondrial iron rings visible as ringed sideroblasts. The X-linked pattern fits transmission through the mother to male relatives. Thalassaemia gives ineffective erythropoiesis without ringed sideroblasts, and parietal cell loss causes megaloblastic rather than sideroblastic change.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.