Work

Impact of glycerol phenylbutyrate on biochemistry and outcomes in paediatric patients with urea cycle disorders: a multicentre case series from Saudi Arabia

Year: 2026

Type: article

Abstract: BACKGROUND: Urea cycle disorders (UCDs) are rare inherited conditions that disrupt ammonia detoxification, leading to hyperammonaemia and potential neurological harm. In Saudi Arabia, high consanguinity rates increase UCD birth incidence. Traditional nitrogen scavengers - sodium benzoate (NaBz) and sodium phenylbutyrate (NaPBA) - are limited by poor palatability, high sodium burden, and large dosing volumes. Glycerol phenylbutyrate (GPB) offers improved pharmacological and practical properties, including slow intestinal hydrolysis, reduced dosing frequency, absence of sodium and propylene glycol, and better tolerability. This study assessed real-world outcomes of GPB in a paediatric UCD population. METHODS: We conducted a retrospective analysis of 37 paediatric patients from three Saudi hospitals. Pre- and post-GPB data were compared for plasma ammonia, hyperammonaemic crises (HACs), HAC-related hospitalisations and durations, growth z-scores, and adverse events. A caregiver survey (n = 15) captured treatment experiences and preferences. RESULTS: GPB significantly reduced routine plasma ammonia levels by 21% (median 72 to 57 µmol/L, p = 0.011), with the proportion of patients above the local reference range dropping from 74% to 42%. Annualised HAC rates fell by 55% (2.2 to 1.0/year), HAC-related hospitalisations by 27% (1.1 to 0.8/year), and annualised HAC-related hospital stays by 24% (3.3 to 2.5 days/year), though these did not reach statistical significance. Growth z-scores showed small, non-significant upward trends (+ 0.2 for height and weight). GPB was well tolerated, with no treatment-related adverse events. All survey respondents (15/15) preferred GPB over NaBz and NaPBA. 100% rated GPB equal or superior in controlling ammonia levels and being easier to adhere to, and 85% found it equal or better for palatability. CONCLUSIONS: GPB improved biochemical control and showed consistent trends toward reduced clinical burden in a real-world paediatric UCD cohort. Although some outcomes were not statistically significant, likely due to sample size and inter-individual variability, the magnitude and direction of change - supported by unanimous patient preference - highlight GPB’s advantages. These findings support its use as a first-line or step-up therapy in paediatric UCDs.

Source: Orphanet Journal of Rare Diseases

DOI: 10.1186/s13023-026-04216-6