Ornithine carbamoyltransferase deficiency

Summary

Ornithine carbamoyltransferase deficiency (MONDO:0010703) is a disease caused by OTC (GenCC Definitive), with 6 cohort genes and 26 clinical trials. Top therapeutic interventions include carglumic acid, sodium acetate, and avalotcagene ontaparvovec.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: OTC (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 732
• Phenotypes (HPO): 29
• Clinical trials: 26

Clinical features

Epidemiology

Prevalence records

7 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.77	Worldwide	Validated
Point prevalence	1-9 / 100 000	1	Europe	Validated
Prevalence at birth	1-9 / 100 000	1.4	Italy	Validated
Prevalence at birth	1-9 / 100 000	1.29	Australia	Validated
Prevalence at birth	1-9 / 100 000	1.6	Finland	Validated
Prevalence at birth	1-9 / 1 000 000	0.88	Canada	Validated
Prevalence at birth	1-9 / 100 000	1.77	United States	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0001399	Hepatic failure	Very frequent (80-99%)
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0001943	Hypoglycemia	Very frequent (80-99%)
HP:0001987	Hyperammonemia	Very frequent (80-99%)
HP:0003355	Aminoaciduria	Very frequent (80-99%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001254	Lethargy	Frequent (30-79%)
HP:0001259	Coma	Frequent (30-79%)
HP:0001298	Encephalopathy	Frequent (30-79%)
HP:0001950	Respiratory alkalosis	Frequent (30-79%)
HP:0002033	Poor suck	Frequent (30-79%)
HP:0002038	Protein avoidance	Frequent (30-79%)
HP:0002039	Anorexia	Frequent (30-79%)
HP:0002045	Hypothermia	Frequent (30-79%)
HP:0002329	Drowsiness	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003218	Oroticaciduria	Frequent (30-79%)
HP:0003572	Low plasma citrulline	Frequent (30-79%)
HP:0005961	Hypoargininemia	Frequent (30-79%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0002572	Episodic vomiting	Occasional (5-29%)
HP:0002908	Conjugated hyperbilirubinemia	Occasional (5-29%)
HP:0003645	Prolonged partial thromboplastin time	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0031258	Delirium	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ornithine carbamoyltransferase deficiency
Mondo ID	MONDO:0010703
EFO	EFO:0007409
MeSH	D020163
OMIM	311250
Orphanet	664
DOID	DOID:9271
ICD-11	1822444026
NCIT	C84957
SNOMED CT	80908008
UMLS	C0268542
MedGen	75692
GARD	0008391
MedDRA	10052450
Is cancer (heuristic)	no

Also known as: OCT deficiency · ornithine carbamoyltransferase deficiency · ornithine carbamoyltransferase deficiency disease · ornithine transcarbamylase deficiency · OTC deficiency · OTCD

Data availability: 732 ClinVar variants · 31 ClinGen variant curations · 5 GenCC gene-disease records · 87 cell lines.

Disease family

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 › urea cycle disorder or inherited hyperammonemia › ornithine carbamoyltransferase deficiency

Related subtypes (9): arginase deficiency, argininosuccinic aciduria, citrullinemia type I, carbamoyl phosphate synthetase I deficiency disease, hyperammonemia due to N-acetylglutamate synthase deficiency, ornithine translocase deficiency, hyperinsulinism-hyperammonemia syndrome, hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency, citrin deficiency

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

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

218 likely benign, 149 uncertain significance, 79 pathogenic, 69 likely pathogenic, 42 conflicting classifications of pathogenicity, 19 benign, 15 benign/likely benign, 9 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
833473	NC_000023.10:g.(?30326313)(41000684_?)del	ATP6AP2	Pathogenic	criteria provided, single submitter
1038367	NM_000531.6(OTC):c.1020_1028del (p.Leu341_Thr343del)	OTC	Pathogenic	criteria provided, single submitter
1066964	NM_000531.6(OTC):c.505C>T (p.Pro169Ser)	OTC	Pathogenic	criteria provided, single submitter
1072591	NM_000531.6(OTC):c.429T>A (p.Tyr143Ter)	OTC	Pathogenic	criteria provided, single submitter
1076888	NC_000023.10:g.(?38210736)(38281703_?)del	OTC	Pathogenic	criteria provided, single submitter
10986	OTC, DEL	OTC	Pathogenic	no assertion criteria provided
10987	NM_000531.6(OTC):c.422G>A (p.Arg141Gln)	OTC	Pathogenic	criteria provided, multiple submitters, no conflicts
10988	NM_000531.6(OTC):c.421C>T (p.Arg141Ter)	OTC	Pathogenic	criteria provided, single submitter
10989	NM_000531.6(OTC):c.332T>C (p.Leu111Pro)	OTC	Pathogenic	no assertion criteria provided
10990	NM_000531.6(OTC):c.646C>G (p.Gln216Glu)	OTC	Pathogenic	no assertion criteria provided
10991	NM_000531.6(OTC):c.460G>T (p.Glu154Ter)	OTC	Pathogenic	criteria provided, single submitter
10992	NM_000531.6(OTC):c.134T>C (p.Leu45Pro)	OTC	Pathogenic	no assertion criteria provided
10993	NM_000531.6(OTC):c.77G>A (p.Arg26Gln)	OTC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
10996	NM_000531.6(OTC):c.717+2T>C	OTC	Pathogenic	no assertion criteria provided
10998	NM_000531.6(OTC):c.387-2A>T	OTC	Pathogenic	criteria provided, single submitter
10999	NM_000531.6(OTC):c.829C>T (p.Arg277Trp)	OTC	Pathogenic	criteria provided, multiple submitters, no conflicts
11000	NM_000531.6(OTC):c.674C>T (p.Pro225Leu)	OTC	Pathogenic	criteria provided, multiple submitters, no conflicts
11001	NM_000531.6(OTC):c.259G>A (p.Glu87Lys)	OTC	Pathogenic	no assertion criteria provided
11002	NM_000531.6(OTC):c.148G>T (p.Gly50Ter)	OTC	Pathogenic	criteria provided, single submitter
11003	NM_000531.6(OTC):c.484G>A (p.Gly162Arg)	OTC	Pathogenic	no assertion criteria provided
11007	NM_000531.6(OTC):c.281G>C (p.Arg94Thr)	OTC	Pathogenic	no assertion criteria provided
11008	NM_000531.6(OTC):c.912G>T (p.Leu304Phe)	OTC	Pathogenic	criteria provided, multiple submitters, no conflicts
11009	NM_000531.6(OTC):c.1033T>G (p.Tyr345Asp)	OTC	Pathogenic	no assertion criteria provided
11010	NM_000531.6(OTC):c.386G>A (p.Arg129His)	OTC	Pathogenic	criteria provided, multiple submitters, no conflicts
11011	NM_000531.6(OTC):c.444G>C (p.Leu148Phe)	OTC	Pathogenic	no assertion criteria provided
11012	NM_000531.6(OTC):c.617T>G (p.Met206Arg)	OTC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11013	NM_000531.6(OTC):c.118C>T (p.Arg40Cys)	OTC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11014	NM_000531.6(OTC):c.119G>A (p.Arg40His)	OTC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1354801	NM_000531.6(OTC):c.614T>C (p.Met205Thr)	OTC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1395169	NM_000531.6(OTC):c.822del (p.Lys276fs)	OTC	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
OTC	Definitive	X-linked	ornithine carbamoyltransferase deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OTC	Orphanet:664	Ornithine transcarbamylase deficiency
ATP6AP2	Orphanet:363654	X-linked parkinsonism-spasticity syndrome
ATP6AP2	Orphanet:93952	X-linked intellectual disability, Hedera type
CYBB	Orphanet:319605	X-linked mendelian susceptibility to mycobacterial diseases
CYBB	Orphanet:379	Chronic granulomatous disease
PHKA1	Orphanet:715	Glycogen storage disease due to muscle phosphorylase kinase deficiency

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OTC	HGNC:8512	ENSG00000036473	P00480	Ornithine transcarbamylase, mitochondrial	gencc,clinvar
SRPX	HGNC:11309	ENSG00000101955	P78539	Sushi repeat-containing protein SRPX	clinvar
ATP6AP2	HGNC:18305	ENSG00000182220	O75787	Renin receptor	clinvar
CYBB	HGNC:2578	ENSG00000165168	P04839	NADPH oxidase 2	clinvar
EFHC2	HGNC:26233	ENSG00000183690	Q5JST6	EF-hand domain-containing family member C2	clinvar
PHKA1	HGNC:8925	ENSG00000067177	P46020	Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OTC	Ornithine transcarbamylase, mitochondrial	Catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline.
SRPX	Sushi repeat-containing protein SRPX	May be involved in phagocytosis during disk shedding, cell adhesion to cells other than the pigment epithelium or signal transduction.
ATP6AP2	Renin receptor	Multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system.
CYBB	NADPH oxidase 2	Catalytic subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)).
EFHC2	EF-hand domain-containing family member C2	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
PHKA1	Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform	Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Complement	1	44.7×	0.067
Enzyme (other)	2	4.0×	0.125
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OTC	Enzyme (other)	yes	2.1.3.3	Orn/put_carbamltrans, Asp/Orn_carbamoylTrfase, Asp_carbamoyltransf_Asp/Orn-bd
SRPX	Complement	yes		Sushi_SCR_CCP_dom, HYR_dom, DUF4174
ATP6AP2	Other/Unknown	no		Renin_rcpt, Renin_r_C, RENR_N
CYBB	Other/Unknown	no		Cyt_b245_heavy_chain, FAD-bd_8, Fe_red_NAD-bd_6
EFHC2	Other/Unknown	no		EF_hand_dom, DM10_dom, EF-hand-dom_pair
PHKA1	Enzyme (other)	yes	2.7.11.19	PHK_A/B_su, 6-hairpin_glycosidase_sf, GH15-like

Expression context

Cohort genes with no expression data: 0.

6 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
jejunal mucosa	1
liver	1
right lobe of liver	1
omental fat pad	1
pericardium	1
peritoneum	1
germinal epithelium of ovary	1
tibia	1
visceral pleura	1
leukocyte	1
monocyte	1
mononuclear cell	1
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1
biceps brachii	1
gastrocnemius	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OTC	139	tissue_specific	marker	jejunal mucosa, right lobe of liver, liver
SRPX	274	ubiquitous	marker	pericardium, peritoneum, omental fat pad
ATP6AP2	295	ubiquitous	marker	visceral pleura, tibia, germinal epithelium of ovary
CYBB	246	broad	marker	monocyte, mononuclear cell, leukocyte
EFHC2	207	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
PHKA1	227	ubiquitous	marker	gastrocnemius, skeletal muscle tissue of rectus abdominis, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYBB	4,117
OTC	2,513
EFHC2	2,428
ATP6AP2	2,236
PHKA1	973
SRPX	790

Intra-cohort edges

A	B	Sources
CYBB	SRPX	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP6AP2	O75787	10
PHKA1	P46020	10
CYBB	P04839	6
OTC	P00480	4
EFHC2	Q5JST6	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SRPX	P78539	85.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 6 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
OTC leader sequence variants cause OTC deficiency	1	2855.0×	0.003	OTC
OTC main chain variants cause OTC deficiency	1	2855.0×	0.003	OTC
Glycogen metabolism	1	475.8×	0.013	PHKA1
Cross-presentation of particulate exogenous antigens (phagosomes)	1	356.9×	0.013	CYBB
Urea cycle	1	219.6×	0.015	OTC
Glycogen breakdown (glycogenolysis)	1	190.3×	0.015	PHKA1
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	1	167.9×	0.015	ATP6AP2
Metabolism of Angiotensinogen to Angiotensins	1	158.6×	0.015	ATP6AP2
RHO GTPases Activate NADPH Oxidases	1	114.2×	0.018	CYBB
Neutrophil degranulation	2	11.5×	0.020	ATP6AP2, CYBB
ROS and RNS production in phagocytes	1	84.0×	0.020	CYBB
Detoxification of Reactive Oxygen Species	1	75.1×	0.021	CYBB
Mitochondrial protein import	1	42.0×	0.035	OTC
VEGFA-VEGFR2 Pathway	1	34.8×	0.037	CYBB
RAC2 GTPase cycle	1	31.7×	0.037	CYBB
Metabolism of carbohydrates and carbohydrate derivatives	1	30.1×	0.037	PHKA1
RAC3 GTPase cycle	1	29.7×	0.037	CYBB
RAC1 GTPase cycle	1	15.3×	0.067	CYBB
Metabolism	1	2.9×	0.302	PHKA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
L-ornithine catabolic process	1	2808.7×	0.007	OTC
eye pigmentation	1	2808.7×	0.007	ATP6AP2
central nervous system maturation	1	1404.3×	0.007	ATP6AP2
obsolete L-arginine biosynthetic process via ornithine	1	1404.3×	0.007	OTC
monoatomic anion homeostasis	1	1404.3×	0.007	OTC
response to biotin	1	1404.3×	0.007	OTC
rostrocaudal neural tube patterning	1	936.2×	0.007	ATP6AP2
L-citrulline biosynthetic process	1	702.2×	0.007	OTC
positive regulation of glycogen catabolic process	1	702.2×	0.007	PHKA1
negative regulation of cell proliferation involved in contact inhibition	1	702.2×	0.007	SRPX
hypoxia-inducible factor-1alpha signaling pathway	1	702.2×	0.007	CYBB
cellular response to L-glutamine	1	702.2×	0.007	CYBB
phagolysosome assembly	1	561.7×	0.008	SRPX
positive regulation of transforming growth factor beta1 production	1	468.1×	0.009	ATP6AP2
ammonium homeostasis	1	401.2×	0.009	OTC
midgut development	1	351.1×	0.010	OTC
head morphogenesis	1	351.1×	0.010	ATP6AP2
response to xenobiotic stimulus	2	23.0×	0.010	OTC, CYBB
response to angiotensin	1	312.1×	0.010	CYBB
Golgi lumen acidification	1	280.9×	0.010	ATP6AP2
response to aldosterone	1	280.9×	0.010	CYBB
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	255.3×	0.010	SRPX
hydrogen peroxide biosynthetic process	1	234.1×	0.010	CYBB
urea cycle	1	216.1×	0.010	OTC
angiotensin maturation	1	216.1×	0.010	ATP6AP2
respiratory burst	1	216.1×	0.010	CYBB
endosomal lumen acidification	1	200.6×	0.010	ATP6AP2
intracellular pH reduction	1	200.6×	0.010	ATP6AP2
cellular response to ethanol	1	175.5×	0.011	CYBB
superoxide metabolic process	1	165.2×	0.011	CYBB

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Sodium Acetate	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 3 of 6 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYBB	NALOXONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYBB	4	4
OTC	0	0
SRPX	0	0
ATP6AP2	0	0
EFHC2	0	0
PHKA1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NALOXONE	4	CYBB
EBSELEN	3	CYBB
SETANAXIB	2	CYBB
ISUZINAXIB	2	CYBB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CYBB	56	Binding:54, Unclassified:1, Functional:1
PHKA1	20	Binding:20
OTC	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OTC	2.1.3.3	ornithine carbamoyltransferase
PHKA1	2.7.11.19	phosphorylase kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

4 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
NALOXONE	4	CYBB
EBSELEN	3	CYBB
SETANAXIB	2	CYBB
ISUZINAXIB	2	CYBB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYBB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	OTC, PHKA1
D	Druggable family + AlphaFold only, no drug	1	SRPX
E	Difficult family or no structure, no drug	2	ATP6AP2, EFHC2

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SRPX	0	CYBB
OTC	3	—
ATP6AP2	0	—
EFHC2	0	—
PHKA1	20	—

Clinical trials & evidence

Clinical trials

Clinical trials: 26.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	14
PHASE2	4
PHASE1/PHASE2	4
PHASE1	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05345171	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Study of DTX301 AAV-Mediated Gene Transfer for Ornithine Transcarbamylase (OTC) Deficiency
NCT05092685	PHASE1/PHASE2	RECRUITING	Halting Ornithine Transcarbamylase Deficiency With Recombinant AAV in ChildrEn
NCT06255782	PHASE1/PHASE2	RECRUITING	An Open-label Study to Investigate ECUR-506 in Male Babies Less Than 9 Months of Age With Neonatal Onset OTC Deficiency
NCT06488313	PHASE2	RECRUITING	A Study to Evaluate the Pharmacodynamics and Safety of ARCT-810 in Participants With OTCD
NCT00718627	PHASE2	COMPLETED	Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders
NCT01599286	PHASE2	COMPLETED	Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
NCT02991144	PHASE1/PHASE2	COMPLETED	Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset Ornithine Transcarbamylase (OTC) Deficiency
NCT03767270	PHASE1/PHASE2	WITHDRAWN	Safety, Tolerability and PK/PD Evaluation of Intravenous Administration of MRT5201 in Patients With OTC Deficiency
NCT05526066	PHASE2	TERMINATED	Study for Adolescents and Adults With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810
NCT06247670	PHASE1	ACTIVE_NOT_RECRUITING	Study of CMP-CPS-001 in Healthy Volunteers and Participants With Abnormal Heterozygous OTC Genotype
NCT04416126	PHASE1	COMPLETED	Safety, Tolerability and Pharmacokinetics of ARCT-810 in Healthy Adult Subjects
NCT04442347	PHASE1	COMPLETED	Phase 1b Study to Assess Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With Ornithine Transcarbamylase Deficiency
NCT03636438	Not specified	ACTIVE_NOT_RECRUITING	Long Term Follow Up to Evaluate DTX301 in Adults With Late-Onset OTC Deficiency
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04612764	Not specified	ACTIVE_NOT_RECRUITING	Liver Disease in Urea Cycle Disorders
NCT04908319	Not specified	RECRUITING	Hepatic Histopathology in Urea Cycle Disorders
NCT06805695	Not specified	RECRUITING	Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
NCT00472732	Not specified	COMPLETED	Neurologic Injuries in Adults With Urea Cycle Disorders
NCT01421888	Not specified	TERMINATED	The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity
NCT01569568	Not specified	COMPLETED	Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI
NCT04248062	Not specified	COMPLETED	Patient and Observer Reported Outcome Measurements in Inborn Errors of Metabolism
NCT04269122	Not specified	COMPLETED	A Study to Assess Plasma Ammonia Time-Normalized Area Under the Curve and Rate of Ureagenesis in Healthy Adult Subjects
NCT04717453	Not specified	TERMINATED	Study to Characterize Rate of Ureagenesis in Patients With Ornithine Transcarbamylase (OTC) Deficiency
NCT04909346	Not specified	TERMINATED	Adeno-Associated Virus (AAV) Antibody Study in Subjects OTC Deficiency, GSDIa, and Wilson Disease
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARGLUMIC ACID	4	1
SODIUM ACETATE	4	1
AVALOTCAGENE ONTAPARVOVEC	1	2