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Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders
- Source :
- Ann Neurol
- Publication Year :
- 2018
-
Abstract
- OBJECTIVE Individuals with urea cycle disorders (UCDs) often present with intellectual and developmental disabilities. The major aim of this study was to evaluate the impact of diagnostic and therapeutic interventions on cognitive outcomes in UCDs. METHODS This prospective, observational, multicenter study includes data from 503 individuals with UCDs who had comprehensive neurocognitive testing with a cumulative follow-up of 702 patient-years. RESULTS The mean cognitive standard deviation score (cSDS) was lower in symptomatic than in asymptomatic (p < 0.001, t test) individuals with UCDs. Intellectual disability (intellectual quotient < 70, cSDS < -2.0) was associated with the respective subtype of UCD and early disease onset, whereas height of the initial peak plasma ammonium concentration was inversely associated with neurocognitive outcomes in mitochondrial (proximal) rather than cytosolic (distal) UCDs. In ornithine transcarbamylase and argininosuccinate synthetase 1 deficiencies, we did not find evidence that monoscavenger therapy with sodium or glycerol phenylbutyrate was superior to sodium benzoate in providing cognitive protection. Early liver transplantation appears to be beneficial for UCDs. It is noteworthy that individuals with argininosuccinate synthetase 1 and argininosuccinate lyase deficiencies identified by newborn screening had better neurocognitive outcomes than those diagnosed after the manifestation of first symptoms. INTERPRETATION Cognitive function is related to interventional and non-interventional variables. Early detection by newborn screening and early liver transplantation appear to offer greater cognitive protection, but none of the currently used nitrogen scavengers was superior with regard to long-term neurocognitive outcome. Further confirmation could determine these variables as important clinical indicators of neuroprotection for individuals with UCDs. ANN NEUROL 2019.
- Subjects :
- 0301 basic medicine
Adult
Glycerol
Male
Pediatrics
medicine.medical_specialty
Adolescent
medicine.medical_treatment
Ornithine transcarbamylase
Liver transplantation
Asymptomatic
Article
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
Cognition
Neonatal Screening
Intellectual disability
medicine
urea cycle disorders
diagnosis
therapy
cognitive function
Humans
Prospective Studies
Glycerol phenylbutyrate
Prospective cohort study
Child
Urea Cycle Disorders, Inborn
Newborn screening
business.industry
Infant, Newborn
Infant
medicine.disease
Mental Status and Dementia Tests
Phenylbutyrates
Liver Transplantation
030104 developmental biology
Cross-Sectional Studies
Neurology
chemistry
Child, Preschool
Female
Neurology (clinical)
medicine.symptom
business
Neurocognitive
030217 neurology & neurosurgery
Follow-Up Studies
Subjects
Details
- ISSN :
- 15318249
- Volume :
- 86
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Annals of neurology
- Accession number :
- edsair.doi.dedup.....21a7a2fa1d043df251db6a0b974b107e