Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders.
Adolescent
Adult
Child
Child, Preschool
Cognition
/ physiology
Cross-Sectional Studies
Female
Follow-Up Studies
Glycerol
/ analogs & derivatives
Humans
Infant
Infant, Newborn
Liver Transplantation
/ methods
Male
Mental Status and Dementia Tests
Neonatal Screening
/ methods
Phenylbutyrates
/ pharmacology
Prospective Studies
Urea Cycle Disorders, Inborn
/ diagnosis
Young Adult
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
19
12
2018
revised:
02
04
2019
accepted:
21
04
2019
pubmed:
25
4
2019
medline:
31
3
2020
entrez:
25
4
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31018246
doi: 10.1002/ana.25492
pmc: PMC6692656
mid: NIHMS1026655
doi:
Substances chimiques
Phenylbutyrates
0
Glycerol
PDC6A3C0OX
glycerol phenylbutyrate
ZH6F1VCV7B
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116-128Subventions
Organisme : NIH HHS
ID : U54HD090257
Pays : United States
Organisme : European Union
ID : 2010 12 01
Pays : International
Organisme : Physician-Scientist Program at University of Heidelberg
Pays : International
Organisme : National Urea Cycle Disorders Foundation
Pays : International
Organisme : Dietmar Hopp Foundation
Pays : International
Organisme : National Center for Advancing Translational Science
Pays : International
Organisme : NICHD NIH HHS
ID : U54 HD061221
Pays : United States
Organisme : Rotenberg Family Fund
Pays : International
Organisme : radiz-Rare Disease Initiative Zurich
Pays : International
Organisme : European Union
ID : EAHC no 2010 12 01
Pays : International
Organisme : Kettering Fund
Pays : International
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
Pays : International
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Organisme : Heidelberg Research Center for Molecular Medicine (HRCMM) in the framework of the Excellence Initiative II of the German Research Foundation
Pays : International
Organisme : Office of Rare Diseases Research
Pays : International
Organisme : NCATS NIH HHS
ID : U2C TR002818
Pays : United States
Organisme : O'Malley Foundation
Pays : International
Organisme : Kindness-for-Kids Foundation
Pays : International
Organisme : NICHD NIH HHS
ID : U54 HD090257
Pays : United States
Investigateurs
Brendan Lee
(B)
Cary O Harding
(CO)
Curtis R Coughlin
(CR)
Cynthia Le Mons
(C)
Dries Dobbelaere
(D)
Elisa Leão Teles
(E)
Elisenda Cortès-Saladelafont
(E)
Florian Gleich
(F)
Francois Eyskens
(F)
Gregory Enns
(G)
Greta N Wilkening
(GN)
Ivo Barić
(I)
J Lawrence Merritt
(J)
Jana Heringer
(J)
Javier Blasco-Alonso
(J)
Jiri Zeman
(J)
Johannes Häberle
(J)
Jolanta Sykut-Cegielska
(J)
Maja Djordjevic
(M)
Mark L Batshaw
(ML)
Marshall Summar
(M)
Peter Freisinger
(P)
Renata C Gallagher
(RC)
Susan A Berry
(SA)
Susan Waisbren
(S)
Tamar Stricker
(T)
Informations de copyright
© 2019 American Neurological Association.
Références
J Inherit Metab Dis. 2005;28(3):407-14
pubmed: 15868473
N Engl J Med. 2007 May 31;356(22):2282-92
pubmed: 17538087
Acta Paediatr. 2008 Oct;97(10):1412-9
pubmed: 18616627
Acta Paediatr. 2008 Oct;97(10):1420-5
pubmed: 18647279
Pediatr Res. 2009 Jul;66(1):96-101
pubmed: 19287347
Mol Genet Metab. 2010;100 Suppl 1:S97-105
pubmed: 20188616
Mol Genet Metab. 2010;100 Suppl 1:S65-71
pubmed: 20202877
Mol Genet Metab. 2010 May;100(1):24-8
pubmed: 20236848
Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):45-53
pubmed: 21312326
Orphanet J Rare Dis. 2011 Jun 20;6:44
pubmed: 21689452
Nat Med. 2011 Nov 13;17(12):1619-26
pubmed: 22081021
J Inherit Metab Dis. 2012 Sep;35(5):777-85
pubmed: 22167275
J Inherit Metab Dis. 2012 Jul;35(4):603-11
pubmed: 22552820
Orphanet J Rare Dis. 2012 May 29;7:32
pubmed: 22642880
Cell. 2012 Jun 8;149(6):1393-406
pubmed: 22658674
J Pediatr. 2013 Feb;162(2):324-9.e1
pubmed: 22901741
Hepatology. 2013 Jun;57(6):2171-9
pubmed: 22961727
Am J Hum Genet. 2014 Mar 6;94(3):453-61
pubmed: 24530203
Mol Genet Metab. 2014 Sep-Oct;113(1-2):105-8
pubmed: 25261246
JIMD Rep. 2015;22:29-38
pubmed: 25701269
J Inherit Metab Dis. 2015 Nov;38(6):1041-57
pubmed: 25875215
J Inherit Metab Dis. 2015 Nov;38(6):1059-74
pubmed: 25875216
J Inherit Metab Dis. 2016 Mar;39(2):219-29
pubmed: 26634836
J Inherit Metab Dis. 2016 Sep;39(5):661-672
pubmed: 27106216
Int J Biostat. 2016 May 1;12(1):45-63
pubmed: 27227717
Orphanet J Rare Dis. 2016 Sep 23;11(1):127
pubmed: 27663197
J Inherit Metab Dis. 2017 May;40(3):357-368
pubmed: 28251416
Pediatr Transplant. 2017 Sep;21(6):null
pubmed: 28608518
Orphanet J Rare Dis. 2017 Jun 15;12(1):111
pubmed: 28619060
Mol Genet Metab. 2017 Nov;122(3):46-53
pubmed: 28916119
J Inherit Metab Dis. 2018 Jul;41(4):657-667
pubmed: 29423830
Genet Med. 2018 Jul;20(7):708-716
pubmed: 29693650
Mol Genet Metab. 2018 Jun;124(2):109-113
pubmed: 29703588
Metab Brain Dis. 2018 Oct;33(5):1517-1523
pubmed: 29948653
PLoS One. 2018 Sep 10;13(9):e0203707
pubmed: 30199544
J Inherit Metab Dis. 2019 Mar;42(2):243-253
pubmed: 30671983
J Inherit Metab Dis. 2019 Jan;42(1):93-106
pubmed: 30740724