title: Erythroblastopenia associated with methylmalonic aciduria. Case report and in vitro studies.
abstract: 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.
authors.affiliation: Laboratory of Hematology, Brugmann University Hospital, Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Corazza
authors.forename: D
authors.initials: D
authors.lastname: Blum
authors.forename: A
authors.initials: A
authors.lastname: Clercx
authors.forename: Y
authors.initials: Y
authors.lastname: Mardens
authors.forename: P
authors.initials: P
authors.lastname: Fondu
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000150:complications*; D000740:Anemia / Q000209:etiology*; D001769:Blood; D002478:Cells, Cultured; D004900:Erythroblasts; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008764:Methylmalonic Acid / Q000494:pharmacology / Q000652:urine*; D011422:Propionates / Q000494:pharmacology
chemical_list: D011422:Propionates; D008764:Methylmalonic Acid; C029658:propionic acid