Background: Very few drugs exist that treat hyperammonemia, specifically PA and MMA. Diet
restrictions and alternate pathway agents are the current primary treatments, but they
frequently fail to prohibit brain damage.
Orthotopic liver transplantation cures the hyperammonemia of urea cycle disorders, but organ
availability is limited and the procedure is highly invasive and requires life-long
A drug that could repair or stimulate a dysfunctional urea cycle such as this would have
several advantages over current therapy. A drug called N-carbamyl-L-glutamate, Carglumic acid
(NCG or Carbaglu)has recently been found to be virtually curative of another urea cycle
defect called NAGS deficiency. In this disorder, treatment with NCG alone normalizes
ureagenesis, blood ammonia and glutamine levels, allows normal protein tolerance and restores
health. Knowledge from this study is being applied to acquired hyperammonemia, specifically
in patients with propionic PA and MMA, to try and improve neurodevelopmental outcomes by
improving the hyperammonemia.
Aims: The overall objective of this project is to determine whether treatment of acute
hyperammonemia with Carglumic acid in propionic acidemia (PA), methylmalonic acidemia (MMA)
changes the long-term outcome of disease and to determine if it is effective in restoring
urine ammonia levels to normal levels.