A new chemical entity, carglumic acid (Carbaglu®), has been registered for the management of hyperammonaemia due to the rare genetic disorders N-acetylglutamate synthase primary deficiency and the organic acidaemias: isovaleric, methylmalonic, and propionic acidaemia.
Ammonia accumulates to toxic levels in these conditions due to an inability to metabolise nitrogen via the urea cycle. Symptoms include vomiting, refusal to eat and progressive lethargy; potentially culminating in seizures, confusion, respiratory distress, cerebral oedema, and coma. Treatments have previously focused on dietary restriction, stimulating alternate pathways to excrete nitrogen, and dialysis.
Carglumic acid (N-carbamoyl-L-glutamic acid) is a structural analogue of N-acetylglutamate, which triggers the urea cycle to eliminate nitrogen and restores ammonia to normal levels within three days. Adverse effects, occurring in up to 13% of patients, include infections, vomiting, abdominal pain, pyrexia, tonsillitis, anaemia, ear infection, diarrhoea, nasopharyngitis, and headache.
The oral tablets should be dispersed in water immediately before administration, and divided up to four times daily. Carglumic acid should be initiated at 100 to 250mg per kg per day and individualised to achieve normal plasma ammonia, and eliminate the need for protein restriction.