Erythroblastopenia associated with methylmalonic aciduria. Case report and in vitro studies

Various cytopenias, including neutropenia, thrombocytopenia and pancytopenia, have been reported in association with inborn errors of branched amino acid metabolism. We report here on a case of anemia associated with erythroblastopenia-that is less frequent in this context-in a neonate with methylmalonic aciduria. We used a semisolid erythroid culture system to investigate the effect on in vitro erythropoiesis of organic acids found in excess in this patient: methylmalonic (MMA) and propionic (PA) acids. First, the addition of 10% serum of the patient to a normal bone marrow progenitor culture suppressed the erythrocyte colony-forming unit growth in comparison to a pool of normal serum, while the addition of a 1:1 mixture of normal and patient serum resulted in an intermediate inhibition. MMA, when added to culture medium, resulted in a moderate inhibition of erythropoiesis only at a higher concentration than observed in our patient or reported in other cases. Conversely, PA showed an inhibitory effect at a concentration commonly observed in methylmalonic aciduria. The same effect was observed when the cells were in the presence of PA only for 72 h and then secondly plated in semisolid culture. Neither MMA nor PA showed any effect on the cell number and viability after a 3-, 4- or 7-day incubation except at the highest concentration tested.