ArticleAnnals of clinical and translational neurology2019
Early prediction of phenotypic severity in Citrullinemia Type 1.
Article in Annals of clinical and translational neurology, 2019. 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 29 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
29 citing papers in PubMed, 48 citations in OpenAlex.
- Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry.International journal of neonatal screening · 2026Article
- Functional profiling of 2,193 ASS1 missense variants: Insights into variant pathogenicity and epistatic interactions in citrullinemia type I.PLoS genetics · 2026Article
- Implications of the FDA's new plausible mechanism framework for the development of a personalized in vivo prime editing platform.American journal of human genetics · 2026Review
- 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
- Dual rare genetic variants: case report of a child with SBIDDS syndrome and citrullinemia type 1.Italian journal of pediatrics · 2026Article
- Trial Readiness: Understanding the Natural History of Rare Diseases.Journal of inherited metabolic disease · 2025Review
- An Explorative Qualitative Study of the Role of a Genetic Counsellor to Parents Receiving a Diagnosis After a Positive Newborn Bloodspot Screening.International journal of neonatal screening · 2025Article
- Article
- Incidence and disease spectrum of inherited metabolic diseases screened by tandem mass spectrometry in Huai'an from 2018 to 2024.Frontiers in pediatrics · 2025Article
- Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises.Pediatric neurology · 2024Observational
- Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?International journal of neonatal screening · 2024Review
- Gut-Brain Axis Modulation of Metabolic Disorders: Exploring the Intertwined Neurohumoral Pathways and Therapeutic Prospects.Neurochemical research · 2024Review
- 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
- Article
- [Evaluation and optimization of newborn screening by structured long-term follow-up-using the example of inherited metabolic diseases].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2023Review
- Functional identification of two novel variants and a hypomorphic variant inFrontiers in genetics · 2023Article
- Case report: Diagnosis of ADCY5-related dyskinesia explaining the entire phenotype in a patient with atypical citrullinemia type I.Frontiers in neurology · 2023Article
- Prenatal diagnosis of citrullinemia type 1; seven families with c.1168GInternational journal of reproductive biomedicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveCitrullinemia type 1 (CTLN1) is an inherited metabolic disease affecting the brain which is detectable by newborn screening. The clinical spectrum is highly variable including individuals with lethal hyperammonemic encephalopathy in the newborn period and individuals with a mild-to-moderate or asymptomatic disease course. Since the phenotypic severity has not been predictable early during the disease course so far, we aimed to design a reliable disease prediction model.
methodsWe used a newly established mammalian biallelic expression system to determine residual enzymatic activity of argininosuccinate synthetase 1 (ASS1; OMIM #215700) in 71 individuals with CTLN1, representing 48 ASS1 gene variants and 50 different, mostly compound heterozygous combinations in total. Residual enzymatic ASS1 activity was correlated to standardized biochemical and clinical endpoints available from the UCDC and E-IMD databases.
resultsResidual enzymatic ASS1 activity correlates with peak plasma ammonium and L-citrulline concentrations at initial presentation. Individuals with 8% of residual enzymatic ASS1 activity or less had more frequent and more severe hyperammonemic events and lower cognitive function than those above 8%, highlighting that residual enzymatic ASS1 activity allows reliable severity prediction. Noteworthy, empiric clinical practice of affected individuals is in line with the predicted disease severity supporting the notion of a risk stratification-based guidance of therapeutic decision-making based on residual enzymatic ASS1 activity in the future.
interpretationResidual enzymatic ASS1 activity reliably predicts the phenotypic severity in CTLN1. We propose a new severity-adjusted classification system for individuals with CTLN1 based on the activity results of the newly established biallelic expression system.
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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.