ArticleAnnals of clinical and translational neurology2022
Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency.
Article in Annals of clinical and translational neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00237315 (Longitudinal Study of Urea Cycle Disorders), which is not on this map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Longitudinal Study of Urea Cycle Disorders
Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Trial
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Longitudinal Changes in Glutamine and Ammonia in Relation to Hyperammonemic Crisis in Urea Cycle Disorders.JIMD reports · 2026Article
- Self-Reported Health-Related Quality of Life (HRQoL) in Adults With Urea Cycle Disorders.Journal of inherited metabolic disease · 2026Observational
- Impact of long-term nitrogen scavenger therapy on clinical outcome in individuals with urea cycle disorders.Scientific reports · 2026Article
- Emerging neurological and cognitive symptoms in patients with late-onset ornithine transcarbamylase deficiency: a narrative review.Metabolic brain disease · 2026Review
- Clinical heterogeneity, genotype, and neurological outcomes in six Palestinian patients with ornithine transcarbamylase deficiency.BMC pediatrics · 2026Article
- Trial Readiness: Understanding the Natural History of Rare Diseases.Journal of inherited metabolic disease · 2025Review
- Development of patient-centric conceptual frameworks for symptoms and impacts of ornithine transcarbamylase deficiency (OTCD).Journal of patient-reported outcomes · 2025Article
- Biochemical Characterization of Disease-Associated Variants of Human Ornithine Transcarbamylase.ACS chemical biology · 2025Article
- Establishment and evaluation of a method for measuring ornithine transcarbamylase activity in micro blood of neonates.Orphanet journal of rare diseases · 2025Article
- Long-term neurodevelopmental outcomes following liver transplantation for metabolic disease-a single centre experience.Journal of inherited metabolic disease · 2025Article
- Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?International journal of neonatal screening · 2024Review
- Article
- Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Impact of supplementation with L-citrulline/arginine after liver transplantation in individuals with Urea Cycle Disorders.Molecular genetics and metabolism · 2024Article
- The functional impact of 1,570 individual amino acid substitutions in human OTC.American journal of human genetics · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveOrnithine transcarbamylase deficiency (OTC-D) is an X-linked metabolic disease and the most common urea cycle disorder. Due to high phenotypic heterogeneity, ranging from lethal neonatal hyperammonemic events to moderate symptoms and even asymptomatic individuals, the prediction of the disease course at an early disease stage is very important to individually adjust therapies such as medical treatment or liver transplantation. In this translational study, we developed a severity-adjusted classification system based on in vitro residual enzymatic OTC activity.
methodsApplying a cell-based expression system, residual enzymatic OTC activities of 71 pathogenic OTC variants were spectrophotometrically determined and subsequently correlated with clinical and biochemical outcome parameters of 119 male individuals with OTC-D (mOTC-D) as reported in the UCDC and E-IMD registries.
resultsIntegration of multiple data sources enabled the establishment of a robust disease prediction model for mOTC-D. Residual enzymatic OTC activity not only correlates with age at first symptoms, initial peak plasma ammonium concentration and frequency of metabolic decompensations but also predicts mortality. The critical threshold of 4.3% residual enzymatic activity distinguishes a severe from an attenuated phenotype.
interpretationResidual enzymatic OTC activity reliably predicts the disease severity in mOTC-D and could thus serve as a tool for severity-adjusted evaluation of therapeutic strategies and counselling patients and parents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.