Abstract

INTRODUCTION

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 phenotype and long-term outcome of pediatric patients with UCD presented at different ages.

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), 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, whereas mental retardation was predominant peculiarity in late-onset UCD. 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 during presentation. However, symptomatic patients with late-onset UCD were often presented without hyperammonemia and metabolic crisis. A cardinal principal of UCD acute and long-term management was restriction of protein intake with appropriate titration of nitrogen scavenging medications and energy intake. Despite these treatment opportunities no improvement of survival was observed in neonatal-onset UCD survival rate (44%(4/9)).

DISCUSSION AND CONCLUSION

Neonatal-onset UCD were generally presented as acute onset hyperammonemia during the newborn period. However, neurological impairment was the most common presentation in the late-onset UCD. The basic principles of diagnosis and treatment need to be reorganizing to improve recognition and outcome in these diseases.