Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial

Introduction Propionic acidemia(PA) and methylmalonic acidemia(MMA) are rare autosomal recessive inborn errorsof metabolismcharacterized by hyperammonemiadue to N-acetylglutamate synthase( NAGS) dysfunction. Carglumic acid(Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemiadue hepatic NAGSdeficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acidin the management of PA and MMA.