Glycerol phenylbutyrate for the maintenance treatment of patients with deficiencies in enzymes of the urea cycle

Introduction: Urea cycle disorders are rare inborn errors of metabolism resulting in the accumulation of ammonia. Over the last 3 decades, the use of alternative nitrogen excretion pathways has been exploited to improve survival and outcomes for urea cycle disorder patients. Areas covered: Early discovered nitrogen scavengers (sodium benzoate, phenylacetate, and phenylbutyrate) are effective in lowering ammonia. However, they have side effects and administration issues that can reduce compliance to therapy and limit optimal outcomes. Glycerol phenylbutyrate, a pro-drug of phenylbutyrate, was developed to improve therapy for patients with urea cycle disorders. Research with glycerol phenylbutyrate has produced the largest body of controlled study data in urea cycle disorder patients to date. Expert opinion: Glycerol phenylbutyrate is better tolerated than sodium phenylbutyrate and enables patients with urea cycle disorders to reach ammonia and glutamine targets. Maintenance of target ammonia levels allows better long-term control in patients with urea cycle defects with reduced neurological sequelae.