A 5-year-old boy with short stature has bilateral radial ray defects including absent thumbs, diffuse hyperpigmentation with cafe-au-lait spots, and pancytopenia with macrocytosis. Mean corpuscular volume is 108 fL and fetal hemoglobin is elevated. Which investigation will confirm the diagnosis?

• A Chromosomal breakage analysis using diepoxybutane ✓
• B Hemoglobin electrophoresis with quantification of HbA2
• C Erythrocyte adenosine deaminase activity
• D Osmotic fragility curve

Explanation

Radial ray anomalies, skin pigmentation changes, short stature, and progressive pancytopenia with macrocytosis and raised fetal hemoglobin define Fanconi anemia. Defective DNA repair produces characteristic chromosomal breaks and radials when peripheral blood lymphocytes are stressed with diepoxybutane or mitomycin C, which confirms the diagnosis. Elevated adenosine deaminase distinguishes Diamond-Blackfan anemia, while osmotic fragility testing applies to hereditary spherocytosis and HbA2 estimation to thalassemia trait.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.