Urea cycle disorders-update.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
24
10
2018
accepted:
15
04
2019
revised:
14
04
2019
pubmed:
22
5
2019
medline:
26
12
2019
entrez:
22
5
2019
Statut:
ppublish
Résumé
The urea cycle is a metabolic pathway for the disposal of excess nitrogen, which arises primarily as ammonia. Nitrogen is essential for growth and life-maintenance, but excessive ammonia leads to life-threatening conditions. The urea cycle disorders (UCDs) comprise diseases presenting with hyperammonemia that arise in either the neonatal period (about 50% of cases) or later. Congenital defects of the enzymes or transporters of the urea cycle cause the disease. This cycle utilizes five enzymes, two of which, carbamoylphosphate synthetase 1 and ornithine transcarbamylase are present in the mitochondrial matrix, whereas the others (argininosuccinate synthetase, argininosuccinate lyase and arginase 1) are present in the cytoplasm. In addition, N-acetylglutamate synthase and at least two transporter proteins are essential to urea cycle function. Severity and age of onset depend on residual enzyme or transporter function and are related to the respective gene mutations. The strategy for therapy is to prevent the irreversible toxicity of high-ammonia exposure to the brain. The pathogenesis and natural course are poorly understood because of the rarity of the disease, so an international registry system and novel clinical trials are much needed. We review here the current concepts of the pathogenesis, diagnostics, including genetics and treatment of UCDs.
Identifiants
pubmed: 31110235
doi: 10.1038/s10038-019-0614-4
pii: 10.1038/s10038-019-0614-4
doi:
Substances chimiques
Ornithine Carbamoyltransferase
EC 2.1.3.3
ARG1 protein, human
EC 3.5.3.1
Arginase
EC 3.5.3.1
Carbamoyl-Phosphate Synthase (Ammonia)
EC 6.3.4.16
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
833-847Références
Hum Gene Ther. 2002 Jan 1;13(1):163-75
pubmed: 11779420
J Neurosci Res. 2001 Dec 1;66(5):899-908
pubmed: 11746417
Eur J Pediatr. 2008 Mar;167(3):305-9
pubmed: 17436013
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3981-6
pubmed: 10097149
Int J Vitam Nutr Res. 2011 Mar;81(2-3):101-7
pubmed: 22139560
Pediatr Res. 1991 Feb;29(2):147-50
pubmed: 2014149
Metabolism. 2012 Nov;61(11):1495-511
pubmed: 22921946
J Pediatr. 1989 Sep;115(3):415-7
pubmed: 2671328
J Pharm Biomed Anal. 2009 Jul 12;49(5):1292-5
pubmed: 19359120
N Engl J Med. 1998 May 7;338(19):1352-7
pubmed: 9571255
Nat Med. 2013 Dec;19(12):1643-8
pubmed: 24240184
Pediatr Res. 1984 Apr;18(4):372-5
pubmed: 6201810
J Pediatr. 2001 Jan;138(1 Suppl):S56-60; discussion S60-1
pubmed: 11148550
Nat Genet. 1999 Jun;22(2):159-63
pubmed: 10369257
Mol Genet Metab. 2009 Apr;96(4):151-7
pubmed: 19211285
Lancet. 1979 Sep 1;2(8140):452-4
pubmed: 89510
J Pediatr. 1992 Aug;121(2):259-61
pubmed: 1640294
Cell Transplant. 2007;16(7):717-28
pubmed: 18019361
N Engl J Med. 1989 Jun 1;320(22):1498-9
pubmed: 2654638
Pediatr Res. 1993 Jan;33(1):77-81
pubmed: 8433866
J Gene Med. 2008 Aug;10(8):890-6
pubmed: 18563850
Pediatrics. 2004 Oct;114(4):e523-6
pubmed: 15466081
Crit Care Clin. 2005 Oct;21(4 Suppl):S37-44
pubmed: 16227114
N Engl J Med. 2005 Nov 3;353(18):1926-33
pubmed: 16267323
Genomics. 1991 May;10(1):126-32
pubmed: 2045097
Metab Brain Dis. 2004 Dec;19(3-4):215-21
pubmed: 15554417
Nat Commun. 2018 Aug 29;9(1):3505
pubmed: 30158522
Prenat Diagn. 2002 Jun;22(6):456-8
pubmed: 12116302
Biochem Biophys Res Commun. 1992 Apr 30;184(2):746-51
pubmed: 1575747
Prog Neurobiol. 2002 Jul;67(4):259-79
pubmed: 12207972
Acta Paediatr. 2008 Oct;97(10):1412-9
pubmed: 18616627
Am J Med Genet. 1995 Jan 16;55(2):247-50
pubmed: 7717428
Mol Genet Metab. 2014 Sep-Oct;113(1-2):127-30
pubmed: 25135652
Mol Ther. 2009 Aug;17(8):1340-6
pubmed: 19384294
Curr Treat Options Neurol. 2010 Mar;12(2):129-41
pubmed: 20842576
J Pediatr. 1991 Dec;119(6):923-8
pubmed: 1720458
Am J Transplant. 2013 Jul;13(7):1830-9
pubmed: 23711238
Mol Genet Metab. 2018 Nov;125(3):241-250
pubmed: 30253962
Brain Res Dev Brain Res. 1995 Dec 21;90(1-2):35-44
pubmed: 8777776
Prenat Diagn. 1996 May;16(5):419-24
pubmed: 8843999
Clin Sci (Lond). 1998 Mar;94(3):313-9
pubmed: 9616266
Gut. 1966 Dec;7(6):631-5
pubmed: 5957514
J Inherit Metab Dis. 2017 Nov;40(6):757-769
pubmed: 28900784
J Biol Chem. 1996 Feb 16;271(7):3639-46
pubmed: 8631974
J Chromatogr B Biomed Sci Appl. 2001 Jul 5;758(1):27-48
pubmed: 11482732
Mol Genet Metab. 2004 Apr;81 Suppl 1:S74-8
pubmed: 15050978
Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):45-53
pubmed: 21312326
Prenat Diagn. 2004 May;24(5):378-83
pubmed: 15164414
Mol Ther. 2006 Jul;14(1):25-33
pubmed: 16677864
Liver Transpl. 2003 Aug;9(8):783-8
pubmed: 12884189
Mol Genet Metab. 2010 May;100(1):24-8
pubmed: 20236848
J Pediatr Surg. 2002 Feb;37(2):159-64
pubmed: 11819191
Am J Med Genet. 1991 May 1;39(2):228-9
pubmed: 2063931
Neurotherapeutics. 2010 Oct;7(4):452-70
pubmed: 20880508
J Child Neurol. 1999 Nov;14 Suppl 1:S4-8
pubmed: 10593560
Lancet. 2001 Jul 7;358(9275):36-8
pubmed: 11454378
Pediatr Transplant. 2014 Feb;18(1):6-15
pubmed: 24283623
J Inherit Metab Dis. 1998;21 Suppl 1:138-50
pubmed: 9686351
J Inherit Metab Dis. 2012 Sep;35(5):777-85
pubmed: 22167275
J Inherit Metab Dis. 1998;21 Suppl 1:6-20
pubmed: 9686341
Biomolecules. 2016 Mar 26;6(2):
pubmed: 27023624
Neurochem Int. 2009 Jul-Aug;55(1-3):113-8
pubmed: 19428814
Eur J Pediatr. 2003 Jun;162(6):417-20
pubmed: 12684898
Orphanet J Rare Dis. 2012 May 29;7:32
pubmed: 22642880
J Inherit Metab Dis. 1998;21 Suppl 1:151-9
pubmed: 9686352
Clin Exp Gastroenterol. 2018 May 24;11:193-215
pubmed: 29872332