ArticleHuman mutation2020
From genotype to phenotype: Early prediction of disease severity in argininosuccinic aciduria.
Article in Human mutation, 2020. 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 15 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
15 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- Trial Readiness: Understanding the Natural History of Rare Diseases.Journal of inherited metabolic disease · 2025Review
- Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?International journal of neonatal screening · 2024Review
- Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors.American journal of human genetics · 2024Article
- 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
- [Evaluation and optimization of newborn screening by structured long-term follow-up-using the example of inherited metabolic diseases].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2023Review
- Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency.Annals of clinical and translational neurology · 2022Article
- Maternal uniparental disomy of chromosome 7 underlying argininosuccinic aciduria and Silver-Russell syndrome.Human genome variation · 2022Article
- Unmet Needs of Parents of Children with Urea Cycle Disorders.Children (Basel, Switzerland) · 2022Article
- Late-onset argininosuccinic aciduria in a 72-year-old man presenting with fatal hyperammonemia.JIMD reports · 2021Article
- Identification of rare variants causing urea cycle disorders: A clinical, genetic, and biophysical study.Journal of cellular and molecular medicine · 2021Article
- Severity-adjusted evaluation of newborn screening on the metabolic disease course in individuals with cytosolic urea cycle disorders.Molecular genetics and metabolism · 2020Article
- Late-onset argininosuccinic aciduria associated with hyperammonemia triggered by influenza infection in an adolescent: A case report.Molecular genetics and metabolism reports · 2020Article
Corrections and comments
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Authors and funding
10 authors at 20 institutions in 12 countries.
Funding
Abstract
Argininosuccinic aciduria (ASA) is an inherited urea cycle disorder and has a highly variable phenotypic spectrum ranging from individuals with lethal hyperammonemic encephalopathy, liver dysfunction, and cognitive deterioration, to individuals with a mild disease course. As it is difficult to predict the phenotypic severity, we aimed at identifying a reliable disease prediction model. We applied a biallelic expression system to assess the functional impact of pathogenic argininosuccinate lyase (ASL) variants and to determine the enzymatic activity of ASL in 58 individuals with ASA. This cohort represented 42 ASL gene variants and 42 combinations in total. Enzymatic ASL activity was compared with biochemical and clinical endpoints from the UCDC and E-IMD databases. Enzymatic ASL activity correlated with peak plasma ammonium concentration at initial presentation and with the number of hyperammonemic events (HAEs) per year of observation. Individuals with ≤9% of enzymatic activity had more severe initial decompensations and a higher annual frequency of HAEs than individuals above this threshold. Enzymatic ASL activity also correlated with the cognitive outcome and the severity of the liver disease, enabling a reliable severity prediction for individuals with ASA. Thus, enzymatic activity measured by this novel expression system can serve as an important marker of phenotypic severity.
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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.