Urea cycle disorder
disease diseaseOn this page
Also known as disorder of urea cycle metabolisminborn disorder of urea cycle metabolism and ammonia detoxificationinborn urea cycle disorderUCDurea cycle disordersurea cycle metabolism disorder
Summary
Urea cycle disorder (MONDO:0004739) is a disease and 46 clinical trials. Top therapeutic interventions include glycerol phenylbutyrate, phenylbutanoic acid, and arginine. A subtype of inborn disorder of amino acid metabolism — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- Clinical trials: 46
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | urea cycle disorder |
| Mondo ID | MONDO:0004739 |
| MeSH | D056806 |
| Orphanet | 79167 |
| DOID | DOID:9267 |
| NCIT | C84785 |
| SNOMED CT | 36444000 |
| UMLS | C0154246 |
| MedGen | 57586 |
| GARD | 0007837 |
| Is cancer (heuristic) | no |
Also known as: disorder of urea cycle metabolism · inborn disorder of urea cycle metabolism and ammonia detoxification · inborn urea cycle disorder · UCD · urea cycle disorders · urea cycle metabolism disorder
Disease family
This is a subtype of inborn disorder of amino acid metabolism. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › urea cycle disorder
Related subtypes (32): disorder of methionine catabolism, inborn serine deficiency, cerebral creatine deficiency syndrome, inborn organic aciduria, gamma-amino butyric acid metabolism disorder, homocystinuria, adenylosuccinate lyase deficiency, systemic primary carnitine deficiency disease, cystathioninuria, hyperlysinemia, Brunner syndrome, glycine encephalopathy, aminoacylase 1 deficiency, adenine phosphoribosyltransferase deficiency, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, inborn disorder of tryptophan metabolism, inborn disorder of proline metabolism, inborn disorder of ornithine metabolism, inborn disorder of amino acid transport, inborn disorder of histidine metabolism, inborn disorder of phenylalanine and tyrosine metabolism, inborn disorder of branched-chain amino acid metabolism, arakawa syndrome 2, 2-methylacetoacetyl CoA thiolase deficiency, albinism, hyperphenylalaninemia due to DNAJC12 deficiency, inborn disorder of the metabolism of sulfur-containing amino acids and hydrogen sulfide, inborn disorder of glycine and serine metabolism, inborn disorder of ornithine, proline and hydroxyproline metabolism, inborn disorder of glutamate/glutamine and aspartate/asparagine metabolism, hyperglycinemia, transient neonatal, tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia
Subtypes (3): 3-methylcrotonyl-CoA carboxylase 1 deficiency, citrullinemia, urea cycle disorder or inherited hyperammonemia
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated or in trials for this disease
1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Status |
|---|---|
| Glycerol Phenylbutyrate | Approved (phase 4) |
Clinical trials & evidence
Clinical trials
Clinical trials: 46.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 27 |
| PHASE2 | 9 |
| PHASE4 | 3 |
| PHASE3 | 3 |
| PHASE1/PHASE2 | 2 |
| PHASE1 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01257737 | PHASE4 | COMPLETED | To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs) |
| NCT02246218 | PHASE4 | COMPLETED | A Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate in Pediatric Subjects Under 2 Years of Age With Urea Cycle Disorders |
| NCT03335488 | PHASE4 | COMPLETED | Study of Glycerol Phenylbutyrate & Sodium Phenylbutyrate in Phenylbutyrate Naïve Patients With Urea Cycle Disorders (UCDs) |
| NCT00947297 | PHASE3 | COMPLETED | Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD) |
| NCT00992459 | PHASE3 | COMPLETED | Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle Disorders |
| NCT01347073 | PHASE3 | COMPLETED | Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs) |
| NCT00345605 | PHASE2 | COMPLETED | Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder |
| NCT00551200 | PHASE2 | COMPLETED | Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle Disorders |
| NCT00718627 | PHASE2 | COMPLETED | Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders |
| NCT00947544 | PHASE2 | COMPLETED | Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle Disorders |
| NCT01195753 | PHASE2 | TERMINATED | Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders |
| NCT01624311 | PHASE2 | COMPLETED | Pilot Study For Hypothermia Treatment In Hyperammonemic Encephalopathy In Neonates And Very Young Infants |
| NCT01765283 | PHASE1/PHASE2 | COMPLETED | Safety Study of HepaStem for the Treatment of Urea Cycle Disorders (UCD) and Crigler-Najjar Syndrome (CN) |
| NCT02489292 | PHASE2 | COMPLETED | Study to Evaluate the Efficacy of HepaStem in Urea Cycle Disorders Paediatric Patients (HEP002) |
| NCT03181828 | PHASE1/PHASE2 | TERMINATED | Manipulating the Gut Microbiome Study |
| NCT03884959 | PHASE2 | WITHDRAWN | A Safety and Efficacy Study of Infusions of HepaStem in Urea Cycle Disorders Pediatric Patients |
| NCT03933410 | PHASE2 | TERMINATED | UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder |
| NCT00986895 | PHASE1 | COMPLETED | A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group |
| NCT03179878 | PHASE1 | COMPLETED | Safety and Tolerability of SYNB1020-CP-001 |
| NCT00237315 | Not specified | RECRUITING | Longitudinal Study of Urea Cycle Disorders |
| NCT02935283 | Not specified | RECRUITING | Neuroimaging and Neuropsychological Outcomes in Urea Cycle Disorders |
| NCT04602325 | Not specified | RECRUITING | Systemic Biomarkers of Brain Injury From Hyperammonemia |
| NCT04612764 | Not specified | ACTIVE_NOT_RECRUITING | Liver Disease in Urea Cycle Disorders |
| NCT04908319 | Not specified | RECRUITING | Hepatic Histopathology in Urea Cycle Disorders |
| NCT05671666 | Not specified | RECRUITING | Ureagenesis Analysis in Healthy Subjects and in Urea Cycle Disorder Patients |
| NCT06664840 | Not specified | NOT_YET_RECRUITING | MyRareDiet A Novel Diet Tracking Tool |
| NCT06904027 | Not specified | RECRUITING | A Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders |
| NCT06953505 | Not specified | RECRUITING | At Home Ammonia Monitoring of Inborn Errors of Ammonia Metabolism |
| NCT00472732 | Not specified | COMPLETED | Neurologic Injuries in Adults With Urea Cycle Disorders |
| NCT01002469 | Not specified | COMPLETED | Study to Evaluate 13 C Isotope Ratio Measurement for Urea Cycle Capacity Assessment |
| NCT01541722 | Not specified | TERMINATED | Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders |
| NCT01549015 | Not specified | COMPLETED | Study in Healthy Subjects, Patients With Urea Cycle Disorders (UCD) and Carriers of UCD Mutations to Evaluate Urea Cycle Function |
| NCT01948427 | Not specified | TERMINATED | Observational Study That Will Collect Information on Patients With Urea Cycle Disorders (UCDs) |
| NCT02051049 | Not specified | COMPLETED | Long-term Safety Follow-up Study of Patients Having Received HepaStem (SAF001) |
| NCT02252770 | Not specified | COMPLETED | Nitric Oxide Supplementation in Argininosuccinic Aciduria |
| NCT02311283 | Not specified | COMPLETED | Pilot Study: Urea Cycle Disorders Practice Patterns and Outcomes Assessment |
| NCT02740153 | Not specified | COMPLETED | PCORI Urea Cycle Disorder Study |
| NCT03064048 | Not specified | COMPLETED | Nitric Oxide Supplementation on Neurocognitive Functions in Patients With ASLD |
| NCT03343756 | Not specified | TERMINATED | HepaStem Long-Term Safety Registry |
| NCT03721367 | Not specified | COMPLETED | Chronic Liver Disease in Urea Cycle Disorders |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| GLYCEROL PHENYLBUTYRATE | 4 | 9 |
| PHENYLBUTANOIC ACID | 4 | 4 |
| ARGININE | 3 | 1 |
| ONTERODRIMER | 2 | 1 |