Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders

作者：Posset Roland^*; Garcia Cazorla Angeles; Valayannopoulos Vassili; Teles Elisa Leao; Dionisi Vici Carlo; Brassier Anais; Burlina Alberto B; Burgard Peter; Cortes Saladelafont Elisenda; Dobbelaere Dries; Couce Maria L; Sykut Cegielska Jolanta; Haberle Johannes; Lund Allan M; Chakrapani Anupam; Schiff Manuel; Walter John H; Zeman Jiri; Vara Roshni; Koelker Stefan

来源：Journal of Inherited Metabolic Disease, 2016, 39(5): 661-672.

DOI：10.1007/s10545-016-9938-9

Background Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation.
Aims Determining the effect of diagnostic and therapeutic interventions on the neurological outcome.
Methods Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry.
Results About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 mu mol/L) best predicted the neurological outcome.
Conclusions Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.

• 出版日期2016-9