Mild/moderate phenotypes in AADC deficiency: Focus on the aromatic amino acid decarboxylase protein.
AADC deficiency
aromatic amino acid decarboxylase
compound heterozygosis
genotype–phenotype correlation
mild/moderate phenotype
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:
21 Aug 2024
21 Aug 2024
Historique:
revised:
06
08
2024
received:
16
03
2024
accepted:
07
08
2024
medline:
21
8
2024
pubmed:
21
8
2024
entrez:
21
8
2024
Statut:
aheadofprint
Résumé
AADC deficiency is a severe neurometabolic inherited rare disorder due to the absence or decrease of dopamine and serotonin levels, causing deep motor and neurodevelopmental impairments. The disease is often fatal in the first decade of life, and pharmacological treatments (dopamine agonists, pyridoxine, and monoamine oxidase inhibitors as the first-line choices) can only alleviate the symptoms. Gene therapy surgery is now available for severe patients in the European Union and the United Kingdom, and follow-up data witness encouraging improvements. In the past few years, mostly due to the increased awareness and knowledge of AADC deficiency, together with newborn screening programs and advancements in methods for genetic diagnosis, the number of mild/moderate phenotypes of AADC deficiency patients has increased to 12% of the total. A review of the genotypes (homozygous/compound heterozygous) of AADC deficiency mild/moderate patients is presented here. The pathogenicity classification of each genetic variant is discussed. Then, we focused on the type of AADC protein possessed by patients and on the predictable structural score of the homodimeric/heterodimeric species of each protein variant. Since the terminology used for genetic and protein variants is the same, we highlighted how it could be misleading. We analyzed the loss-of-function as a fold-change decrease of activity of the recombinant purified AADC enzyme(s) theoretically synthesized by mild/moderate patients. A minimal residual k
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : PTC Therapeutics, IIS Grant
Organisme : Ministero dell'Università e della Ricerca
ID : PRIN2022code
Organisme : Ministero dell'Università e della Ricerca
ID : 2022BTMTP8
Organisme : Università degli Studi di Verona
ID : FUR2022
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca, National Recovery and Resilience Plan (NRRP)), and by #NEXTGENERATIONEU (NGEU) project MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022) (Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP))
Informations de copyright
© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
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