Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects.
arginine
argininosuccinate lyase
argininosuccinic aciduria
creatine
nitric oxide
nitrosative stress
oxidative stress
urea cycle
Journal
Journal of inherited metabolic disease
ISSN: 1573-2665
Titre abrégé: J Inherit Metab Dis
Pays: United States
ID NLM: 7910918
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
18
11
2018
accepted:
20
12
2018
pubmed:
7
2
2019
medline:
25
8
2020
entrez:
7
2
2019
Statut:
ppublish
Résumé
The first patients affected by argininosuccinic aciduria (ASA) were reported 60 years ago. The clinical presentation was initially described as similar to other urea cycle defects, but increasing evidence has shown overtime an atypical systemic phenotype with a paradoxical observation, that is, a higher rate of neurological complications contrasting with a lower rate of hyperammonaemic episodes. The disappointing long-term clinical outcomes of many of the patients have challenged the current standard of care and therapeutic strategy, which aims to normalize plasma ammonia and arginine levels. Interrogations have raised about the benefit of newborn screening or liver transplantation on the neurological phenotype. Over the last decade, novel discoveries enabled by the generation of new transgenic argininosuccinate lyase (ASL)-deficient mouse models have been achieved, such as, a better understanding of ASL and its close interaction with nitric oxide metabolism, ASL physiological role outside the liver, and the pathophysiological role of oxidative/nitrosative stress or excessive arginine treatment. Here, we present a collaborative review, which highlights these recent discoveries and novel emerging concepts about ASL role in human physiology, ASA clinical phenotype and geographic prevalence, limits of current standard of care and newborn screening, pathophysiology of the disease, and emerging novel therapies. We propose recommendations for monitoring of ASA patients. Ongoing research aims to better understand the underlying pathogenic mechanisms of the systemic disease to design novel therapies.
Substances chimiques
Argininosuccinate Lyase
EC 4.3.2.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1147-1161Subventions
Organisme : Medical Research Council
ID : MR/S019111/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N019075/1
Pays : United Kingdom
Informations de copyright
© 2019 SSIEM.
Références
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