Aromatic L-amino acid decarboxylase deficiency in countries in the Middle East: a case series and literature review.
AADC deficiency
Case report
Delayed diagnosis
Developmental delay
Whole exome sequencing
Journal
European journal of pediatrics
ISSN: 1432-1076
Titre abrégé: Eur J Pediatr
Pays: Germany
ID NLM: 7603873
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
21
09
2022
accepted:
16
02
2023
revised:
15
02
2023
medline:
12
6
2023
pubmed:
18
3
2023
entrez:
17
3
2023
Statut:
ppublish
Résumé
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited neurometabolic disorder that can lead to severe physical and developmental impairment. This report includes 16 patients from the Middle East and is the largest series of patients with confirmed AADC deficiency from this region reported to date. The patients displayed a range of signs and symptoms at presentation and almost all failed to reach major motor milestones. Missed and delayed diagnoses were common leading to the late introduction of targeted treatments. Eight unique variants were identified in the DDC gene, including six missense and two intronic variants. A previously undescribed variant was identified: an intronic variant between exons 13 and 14 (c.1243-10A>G). The patients were mostly treated with currently recommended medications, including dopamine agonists, vitamin B6, and monoamine oxidase inhibitors. One patient responded well, but treatment outcomes were otherwise mostly limited to mild symptomatic improvements. Five patients had died by the time of data collection, confirming that the condition is associated with premature mortality. There is an urgent need for earlier diagnosis, particularly given the potential for gene therapy as a transformative treatment for AADC deficiency when provided at an early age. Conclusions: Delays in the diagnosis of AADC deficiency are common. There is an urgent need for earlier diagnosis, particularly given the potential for gene therapy as a transformative treatment for AADC deficiency when provided at an early age. What is Known: • Aromatic L-amino acid decarboxylase deficiency is a rare neurometabolic disorder that can lead to severe physical and developmental impairment. • Currently recommended medications provide mostly mild symptomatic improvements. What is New: • The clinical presentation of sixteen patients with confirmed AADC deficiency varied considerably and almost all failed to reach major motor milestones. • There is an urgent need for earlier diagnosis, given the potential for gene therapy as a transformative treatment for AADC deficiency when provided at an early age.
Identifiants
pubmed: 36928758
doi: 10.1007/s00431-023-04886-5
pii: 10.1007/s00431-023-04886-5
pmc: PMC10257624
doi:
Substances chimiques
Aromatic-L-Amino-Acid Decarboxylases
EC 4.1.1.28
Dopamine Agonists
0
DDC protein, human
EC 4.1.1.28
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2535-2545Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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