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

INTRODUCTION: Urea cycle disorders (UCD) still have poor neurological outcome despite early diagnosis and treatment. We aimed to present the neurological outcome of UCD patients and to determine the simple and accessible main factors affecting the neurological outcome.
METHODS: This is a descriptive cross-sectional study conducted in two pediatric metabolism centers in 29 patients from 25 unrelated families who were followed and diagnosed with UCD based on clinical presentation, neurological parameters, biochemical measurements, and molecular analysis.
RESULTS: Within the study population, the most common diagnosis was ASSD in 13 (44.82%) patients, followed by NAGSD in five patients (17.24%), OTCD in four patients (13.79%), ARG1D in three patients (10.34%), CPS1D in three patients (10.34%), and ASLD in one patient (3.44%). Peak ammonia levels were observed to be significantly higher in patients with delayed milestones and patients who had Denver II <-2SDS 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 >500μmol/L (n=18). Patients with abnormal neurological parameters had a significantly higher mean hyperammonemic episodes per year. Extracorporeal detoxification was received to eight patients, combination with therapeutic hypothermia in two patients. However, rapid regression was observed in brain edema in those who underwent therapeutic hypothermia.
DISCUSSION AND CONCLUSION: Our study emphasizes the effect of peak ammonia levels and the frequency of hyperammonemic episodes on the neurological outcome. 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.