ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
Expanding the clinical and genetic spectrum of CAD deficiency: an epileptic encephalopathy treatable with uridine supplementation.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
- An Optimized Diagnostic Approach for Adults With Suspected Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Glycosylation disorders in pediatric epilepsy: pathophysiology, imaging and precision therapy.Frontiers in neurology · 2026Review
- Evaluation, Diagnosis, and Treatment of Concomitant Movement Disorders in Genetic Epilepsies.Epilepsy currents · 2025Review
- Epileptic encephalopathy in a young Bengal cat caused by CAD deficiency.Scientific reports · 2025Article
- Epileptic Encephalopathy Related to CAD Deleterious Variants-A Case Series.Diseases (Basel, Switzerland) · 2025Article
- Novel CAD gene mutations in a boy with developmental and epileptic encephalopathy 50 with dramatic response to uridine therapy: a case report and a review of the literature.BMC pediatrics · 2024Review
- Beyond genetics: Deciphering the impact of missense variants in CAD deficiency.Journal of inherited metabolic disease · 2023Article
- A Tailored Strategy to Crosslink the Aspartate Transcarbamoylase Domain of the Multienzymatic Protein CAD.Molecules (Basel, Switzerland) · 2023Article
- How to proceed after "negative" exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques.Journal of inherited metabolic disease · 2022Review
- Nutrition interventions in congenital disorders of glycosylation.Trends in molecular medicine · 2022Review
- Uridine monophosphate (UMP)-responsive developmental and epileptic encephalopathy: A case report of two siblings and a review of literature.Molecular genetics and metabolism reports · 2022Article
- Deciphering CAD: Structure and function of a mega-enzymatic pyrimidine factory in health and disease.Protein science : a publication of the Protein Society · 2021Review
- Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app.Orphanet journal of rare diseases · 2021Review
- Metabolic Seizures.Frontiers in neurology · 2021Review
- [Molecular medicine: pathobiochemistry as the key to personalized treatment of inherited diseases].Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde · 2021Review
- Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing.Frontiers in genetics · 2021Article
- Case Report: Rapid Treatment of Uridine-Responsive Epileptic Encephalopathy Caused by CAD Deficiency.Frontiers in pharmacology · 2020Article
- Molecular diagnostic yield of whole-exome sequencing in Saudi autistic children with epilepsy.International journal of health sciencesArticle
Corrections and comments
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Authors and funding
23 authors at 16 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeBiallelic CAD variants underlie CAD deficiency (or early infantile epileptic encephalopathy-50, [EIEE-50]), an error of pyrimidine de novo biosynthesis amenable to treatment via the uridine salvage pathway. We further define the genotype and phenotype with a focus on treatment.
methodsRetrospective case series of 20 patients.
resultsOur study confirms CAD deficiency as a progressive EIEE with recurrent status epilepticus, loss of skills, and dyserythropoietic anemia. We further refine the phenotype by reporting a movement disorder as a frequent feature, and add that milder courses with isolated developmental delay/intellectual disability can occur as well as onset with neonatal seizures. With no biomarker available, the diagnosis relies on genetic testing and functional validation in patient-derived fibroblasts. Underlying pathogenic variants are often rated as variants of unknown significance, which could lead to underrecognition of this treatable disorder. Supplementation with uridine, uridine monophosphate, or uridine triacetate in ten patients was safe and led to significant clinical improvement in most patients.
conclusionWe advise a trial with uridine (monophosphate) in all patients with developmental delay/intellectual disability, epilepsy, and anemia; all patients with status epilepticus; and all patients with neonatal seizures until (genetically) proven otherwise or proven unsuccessful after 6 months. CAD deficiency might represent a condition for genetic newborn screening.
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