Presentation and management of classical urea cycle disorders: lessons from our experience

Objective: The urea cycle disorders (UCD) are inherited deficiencies of the enzymes or transport molecules involved in the cellular excretion of excess ammonia produced during protein metabolism. The aim of this study was to evaluate the clinical characteristics and long-term outcome of pediatric patients with UCD seen during childhood. Methods: Clinical characteristics in 13 patients with classical UCD (carbamoyl phosphate synthetase I deficiency (n= 4), argininosuccinate lyase deficiency (n= 4), argininosuccinate synthetase deficiency (n= 3), arginase deficiency (n= 1), and ornithine transcarbamylase deficiency (n= 1)) were defined. The term "neonatal-onset" UCD was used if symptoms occurred within 28 days of life, and "late-onset" if symptoms started after that period. Results: The majority of patients (n= 9) presented with acute metabolic crisis during newborn period. Core clinical phenotype in neonatal-onset UCD included sepsis-like neonatal crisis revealed in patients within 28 days after birth, whereas mental retardation was predominant peculiarity in late-onset UCD emerging more than 28 days after birth. Vomiting and hypotonia were frequently reported in neonatal-onset UCD, and epilepsy with/without movement disorder was found in late-onset UCD patients. For patients with neonatal-onset UCD hyperammonemia was more severe at first diagnosis of the disease, and remained near upper limits of normal during the follow-up period. However, hyperammonemia and metabolic crisis have been reported lomber spinal stenoz frequently in symptomatic patients. A cardinal principal of UCD in acute and long-term management of UCD. Despite these evolving treatment opportunities, still higher mortality rates were found in neonatal-onset UCD (44% (4/9)). Conclusion: Neonatal-onset UCD were generally presents itself as acute onset hyperammonemia during the newborn period. However, neurological manifestations were reportedly more diagnostic in the late-onset UCD. It has been concluded that the basic principles of diagnosis and treatment need to be reorganized to improve recognition and outcome in these diseases.