Aplastic anaemia and bone-marrow failure: Case

This boy has the classic presentation of Fanconi anaemia declaring itself as severe aplastic anaemia. The short stature, the café-au-lait spots, the absent thumbs with the hypoplastic radii, and the macrocytosis of 104 femtolitres are the physical and laboratory signs of the inherited syndrome, and the hypocellular marrow of 12 percent with the pancytopenia is the marrow failure. The examiner is testing whether the fellow recognises the inherited syndrome, confirms it with the right test, plans the transplant with the right conditioning, and counsels the family on the inheritance and the cancer risk. ^[9]

Confirming the diagnosis

The first task is to confirm the Fanconi anaemia, and the test is the diepoxybutane chromosomal breakage test. The test is performed on the peripheral blood lymphocytes, and it adds a cross-linking agent and counts the chromosomal breaks and the radial figures, which are markedly increased in Fanconi anaemia and normal in the acquired disease. The next-generation sequencing panel for the FANC genes confirms the mutation and identifies the specific gene, which matters for the family counselling and the prenatal diagnosis. The boy meets the Camitta criteria for severe aplastic anaemia, with a cellularity of 12 percent under 25 percent and all three blood thresholds met, and the mean corpuscular volume of 104 femtolitres and the raised fetal haemoglobin are the quiet signs of the inherited syndrome that the fellow should not miss. ^[9]

The distinction from the acquired disease is the single most important step, because the transplant conditioning differs. A child with the acquired aplastic anaemia is transplanted with the cyclophosphamide based regimen, and a child with Fanconi anaemia is transplanted with the reduced intensity fludarabine based regimen, because the DNA repair defect makes the child exquisitely sensitive to the standard chemotherapy and radiation. The fellow who plans a transplant for this boy holds the conditioning until the diepoxybutane test returns, because the standard regimen in unrecognised Fanconi anaemia can be fatal. ^[9]