Evaluation of the Neurodevelopmental Status for Urea Cycle Disorders: Based on Clinical Experience

Abstract

Aim: Urea cycle disorders (UCD) still have poor neurological outcomes despite early diagnosis and treatment. We aimed to present the neurological outcomes of UCD patients and to determine the main simple and accessible factors affecting these outcomes. Materials and Methods: This was a descriptive cross-sectional study conducted in two pediatric metabolism centers on 29 patients from 25 unrelated families who were diagnosed and followed with UCD based on clinical presentation, neurological parameters, biochemical measurements, and molecular analysis. Results: Within the study population, the most common diagnosis was argininosuccinate synthase deficiency in 13 (44.82%) patients, followed by N-acetylglutamate synthase deficiency in five patients (17.24%), ornithine transcarbamylase deficiency in four patients (13.79%), arginase 1 deficiency in three patients (10.34%), carbamoyl phosphate synthase 1 deficiency in three patients (10.34%), and argininosuccinate lyase deficiency in one patient (3.44%). Peak ammonia levels were observed to be significantly higher in those patients with delayed milestones and patients who had Denver II <-2 standard deviation score results (p=0.032, p=0.026). Effect sizes were large in both groups. Delayed milestones were noted in 17 (94.4%) of the cases with peak ammonia >500 μmol/L (n=18). Those patients with abnormal neurological parameters had a significantly higher mean number of hyperammonemic episodes per year. Extracorporeal detoxification was given to eight patients, in combination with therapeutic hypothermia in two patients. Rapid regression was observed in brain edema in those who underwent therapeutic hypothermia. Conclusion: Our study emphasizes the effect of peak ammonia levels and the frequency of hyperammonemic episodes on neurological outcomes. There were still poor neurocognitive outcomes despite extracorporeal detoxification. This highlights the need to reassess current treatment strategies, including the threshold for starting extracorporeal detoxification if ammonia levels exceed 500 µmol/L. The use of therapeutic hypothermia by experienced teams may be promising due to its brain edema-reducing effects.