Uridine-responsive epileptic encephalopathy due to inherited variants in CAD: A Tale of Two Siblings.
Aspartate Carbamoyltransferase
/ genetics
Atrophy
/ pathology
Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)
/ genetics
Cerebellar Diseases
/ drug therapy
Child
Child, Preschool
Developmental Disabilities
/ drug therapy
Dihydroorotase
/ genetics
Disease Progression
Drug Resistant Epilepsy
/ drug therapy
Female
Humans
Male
Pedigree
Siblings
Uridine
/ administration & dosage
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
04
11
2020
accepted:
10
11
2020
pubmed:
27
1
2021
medline:
3
11
2021
entrez:
26
1
2021
Statut:
ppublish
Résumé
We report two siblings with intractable epilepsy, developmental regression, and progressive cerebellar atrophy due to biallelic variants in the gene CAD. For the affected girl, uridine started at age 5 resulted in dramatic improvements in seizure control and development, cessation of cerebellar atrophy, and resolution of hematological abnormalities. Her older brother had a more severe course and only modest response to uridine started at 14 years old. Treatment of this progressive condition via uridine supplementation provides an example of precision diagnosis and treatment using clear outcome measures and biomarkers to monitor efficacy.
Identifiants
pubmed: 33497533
doi: 10.1002/acn3.51272
pmc: PMC7951104
doi:
Substances chimiques
CAD trifunctional enzyme
0
Aspartate Carbamoyltransferase
EC 2.1.3.2
Dihydroorotase
EC 3.5.2.3
Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)
EC 6.3.5.5
Uridine
WHI7HQ7H85
Types de publication
Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
716-722Subventions
Organisme : NINDS NIH HHS
ID : K08 NS118107
Pays : United States
Organisme : NINDS NIH HHS
ID : K08NS118107-01
Pays : United States
Informations de copyright
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Front Neurol. 2020 Feb 05;11:64
pubmed: 32117025
Curr Med Chem. 2016;23(14):1408-31
pubmed: 27063261
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Hum Mol Genet. 2015 Jun 1;24(11):3050-7
pubmed: 25678555
Nature. 2019 Jul;571(7766):505-509
pubmed: 31243369
Genet Med. 2020 Oct;22(10):1598-1605
pubmed: 32461667
Brain. 2017 Feb;140(2):279-286
pubmed: 28007989