Abstract
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.
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aspartate Carbamoyltransferase / genetics*
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Atrophy / pathology
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Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / genetics*
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Cerebellar Diseases / drug therapy
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Cerebellar Diseases / genetics
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Cerebellar Diseases / pathology
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Child
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Child, Preschool
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Developmental Disabilities / drug therapy
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Developmental Disabilities / genetics
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Dihydroorotase / genetics*
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Disease Progression
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Drug Resistant Epilepsy / drug therapy*
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Drug Resistant Epilepsy / genetics*
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Female
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Humans
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Male
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Pedigree
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Siblings
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Uridine / administration & dosage
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Uridine / pharmacology*
Substances
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CAD trifunctional enzyme
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Aspartate Carbamoyltransferase
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Dihydroorotase
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Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)
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Uridine