Long-term N-carbamylglutamate treatment of hyperammonemia in patients with classic organic acidemias

BACKGROUND: Classic organic acidurias (OAs) usually characterized by recurrent episodes of acidemia, ketonuria, and hyperammonemia leading to coma and even death if left untreated. Acute hyperammonemia episodes can be treated effectively with N-carbamylglutamate (NCG). The effect of the long-term efficacy of N-carbamylglutamate is little known. MATERIAL-METHODS: This retrospective study was conducted at Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Pediatric Nutrition and Metabolism Clinic between January 2012 to January 2018. Patients with classic OAs were enrolled in the study. Patients' ammonia levels, hospitalization needs, hyperammonemia episodes, and management of hyperammonemia were recorded. NCG usage for more than consecutively 15 days was considered as a long-term treatment. RESULTS: Twenty-one patients, consisting of eleven patients with methylmalonic acidemia (MMA) and ten patients with propionic acidemia (PA) were eligible for the study. N-carbamylglutamate was used as ammonia scavenger for a total of 484 months with a median period of 23 months (min-max: 3–51 months) in all patients. A significant decrease in plasma ammonia levels was detected during long term NCG treatment (55.31 ± 13.762 μmol/L) in comparison with pre NCG treatment period (69.64 ± 17.828 μmol/L) (p = 0.021). Hospitalization required hyperammonemia episodes decreased with NCG treatment (p = 0.013). In addition, hyperammonemia episodes were also successfully treated with NCG (p = 0.000). Mean initial and final ammonia levels at the time of hyperammonemia episodes were 142 ± 46.495 μmol/L and 42.739 ± 12.120 μmol/L, respectively. The average NCG dosage was 85 mg/kg/day (range 12.5–250 mg/kg/day). No apparent side effects were observed. CONCLUSION: N-Carbamylglutamate may be deemed an effective and safe treatment modality in the chronic management of hyperammonemia in patients with PA and MMA.