Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre.

In urea cycle disorders (UCDs) ammonia scavenger drugs, usually sodium-based, have been the mainstay of treatment. Increasingly, glycerol phenylbutyrate (GPB, Ravicti®) is being used but scant real-world data exist regarding clinical outcomes. A retrospective study of UCD patients initiated on or switched to GPB was performed at a UK centre. Data on population characteristics, treatment aspects, laboratory measurements, and clinical outcomes were collected before and after patients started GPB with a sub-group analysis undertaken for patients with ≥12 months of data before and after starting GPB. UCDs included arginosuccinate synthetase deficiency ( = 8), arginosuccinate lyase deficiency ( = 6), ornithine carbamoyltransferase deficiency ( = 3), and carbamoyl phosphate synthetase 1 deficiency ( = 3). In the sub-group analysis ( = 11), GPB resulted in lower plasma ammonia (31 vs. 41 μmol/L,  = 0.037), glutamine (670 vs. 838 μmol/L,  = 0.002), annualised hyperammonaemic episodes (0.2 vs. 1.9,  = 0.020), hospitalisations (0.5 vs. 2.2,  = 0.010), and hyperammonaemic episodes resulting in hospitalisation (0.2 vs. 1.6,  = 0.035) reflecting changes seen in the whole group. Overall, patients exposed to sodium and propylene glycol levels above UK daily limits reduced by 78% and 83% respectively. Mean levels of branched chain amino acids, haemoglobin, and white cell count were unchanged. Two adverse drug reactions (pancytopenia, fatigue/appetite loss) resolved without GPB discontinuation. Patients/families preferred GPB for its lower volume, greater palatability and easier administration. GPB appeared to improve biochemical measures and clinical outcomes. The causes are multi-factorial and are likely to include prolonged action of GPB and its good tolerability, even at higher doses, facilitating tighter control of ammonia.