1. Adolescent-onset epilepsy and deterioration associated with CAD deficiency: A case report.
- Author
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Silva S, Rosas M, Guerra B, Muñoz M, Fujita A, Sakamoto M, and Matsumoto N
- Subjects
- Humans, Female, Adolescent, Dihydroorotase genetics, Mutation, Missense, Status Epilepticus genetics, Cognitive Dysfunction genetics, Age of Onset, Aspartate Carbamoyltransferase, Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing), Epilepsy genetics
- Abstract
Introduction: CAD (MIM*114010) encodes a large multifunctional protein with the enzymatic activity of the first three enzymes initiating and controlling the de novo pyrimidine biosynthesis pathway. Biallelic pathogenic variants in CAD cause the autosomal recessive developmental and epileptic encephalopathy 50 (MIM #616457) or CAD deficiency presenting with epilepsy, status epilepticus (SE), neurological deterioration and anemia with anisopoikilocytosis. Mortality is around 9% of patients, mainly related to the no use of its specific treatment with uridine. Majority of reported cases have an early onset during infancy, with some few starting later in childhood., Case Report: Here we report a deceased female patient with CAD deficiency whose epilepsy started at 14 years. She showed a rapid neurologic deterioration including cognitive decline, electroencephalographic background slowing which later evolved to a fatal refractory SE and supra and infratentorial atrophy on neuroimaging. Anemia developed after SE onset., Methods and Results: her post-mortem whole exome sequencing identified biallelic missense variants in CAD (NM_004341.5): c.[2944G > A];[5366G > A] p.[(Asp982Asn)];[(Arg1789Gln)]. Our review of twenty-eight reported cases (2015-2023) revealed an epilepsy age onset from neonatal period to 7 years and the SE prevalence of 46 %., Discussion: With our case, we highlight the relevance of suspecting this treatable condition in older patients and in SE with no evident etiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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