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ORPHA:927

Hyperammonemia due to N-acetylglutamate synthase deficiency

low confidenceDisorder

Also known as: NAGS deficiency

Publications

3,442

Trials

1

Interventional, condition-specific

Researchers

1,029

Distinct authors in sample

Gene link

NAGS

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A rare disorder of urea cycle metabolism causing a deficit of ammonia detoxification and arginine synthesis, and characterized by of variable severity. Manifestations range from presentation of poor feeding, vomiting, lethargy, tachypnea, convulsions and coma to adult-onset headaches, hazy gastrointestinal symptoms, , behavioral/psychiatric problems, confusion and lethargy.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (1)

hyperammonemia due to N-acetylglutamate synthase deficiency

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

5/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — NAGS

  2. LiteraturePresent

    3,442 matched papers (2,173 in last 10 years) Source

  3. Phenotype characterisedPresent

    63 HPO annotations (e.g. Emotional lability; Confusion; Drowsiness) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationPartial

    1 FDA designation (none yet with FDA orphan-indication approval) — e.g. carglumic acid Source

  6. Interventional trialPresent

    1 matched on ClinicalTrials.gov (1 recruiting in sample)

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (NAGS).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

63

Associated phenotypes · MONDO:0009377

  • Emotional lability
  • Confusion
  • Drowsiness
  • Poor speech
  • Insomnia

Showing 5 of 63 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

Monarch fetch 2026-07-27

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

1

Designation · no FDA orphan-indication approval yet

  • FDA carglumic acid (Carbaglu)N-acetylglutamate synthetase deficiency · 1998-01-20

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

1

Drugs / clinical candidates · MONDO_0009377

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

3,442

3,442 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

3,442 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

2,173 in the last 10 years · low confidence

Phrase hits: 200 · MeSH hits: 1

Open Europe PMC search

Who's working on it?

1,029

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Tuchman M35 papers · 2021

    Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC 20010, USA. Mtuchman@cnmc.org.

    Papers in Europe PMC
  2. 02
    Caldovic L26 papers · 2024

    Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC 20010, USA. LCaldovic@childrensnational.org.

    Papers in Europe PMC
  3. 03
    Morizono H16 papers · 2024

    Children's Research Institute, Children's National Medical Center, The George Washington University, 111 Michigan Ave NW, Washington, DC 20010, USA.

    Papers in Europe PMC
  4. 04
    Häberle J15 papers · 2024

    University Children's Hospital Zurich and Children's Research Centre, Zurich, 8032, Switzerland. Johannes.Haeberle@kispi.uzh.ch

    Papers in Europe PMC
  5. 05
    Shi D13 papers · 2018

    Center for Genetic Medicine Research and Department of Integrative Systems Biology, Children's National Medical Center, The George Washington University, Washington, DC, United States of America. dshi@cnmcresearch.org

    Papers in Europe PMC
  6. 06
    Yudkoff M12 papers · 2021

    Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

    Papers in Europe PMC
  7. 07
    Ah Mew N11 papers · 2021

    Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC 20010, USA.

    Papers in Europe PMC
  8. 08
    Allewell NM7 papers · 2015

    Department of Cell Biology and Molecular Genetics, College of Computer, Mathematical, and Natural Sciences, University of Maryland, College Park, MD 20742, USA. allewell@umd.edu.

    Papers in Europe PMC
  9. 09
    Nissim I7 papers · 2014

    Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA.

    Papers in Europe PMC
  10. 10
    Rubio V7 papers · 2024

    Instituto de Biomedicina de Valencia del Consejo Superior de Investigaciones Científicas (IBV-CSIC), Jaime Roig 11, 46010 Valencia, Spain.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

1

interventional trials for this specific condition

1 interventional trial matched this specific condition name; 1 currently recruiting in our sample.

Data as of 9 September 2026 · last trial check 20 August 2026

1 interventional trial — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 80.1th percentile).

low confidence · 80.1th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

1 interventional trials matched after quoted-phrase search and title/condition post-filter.

Observational and natural-history studies

3 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-27

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Hyperammonemia due to N-acetylglutamate synthase deficiency — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Urea cycle disorder as a category (Groups 1 and 2), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

Group 1 — one-time curative treatment

Up to ₹50 lakh per patient

Financial support for treatment at notified Centres of Excellence (figures evolved from the original ₹20 lakh Group-1 ceiling).

Policy figures change. Verify current MoHFW / CoE guidance before relying on any amount. Verify

Group 2 — long-term / lifelong lower-cost interventions

NPRD envisages State Government support for dietary formulae, hormones, and other lower-cost interventions. This is a different route from the central CoE ₹50 lakh pathway; ask your state health department and a CoE which channel applies.

Central CoE funding may also apply depending on current rules — confirm with a notified Centre of Excellence. Do not assume the ₹50 lakh ceiling covers Group 2 by default. Verify

Centres of Excellence (15)
  • All India Institute of Medical Sciences (AIIMS) — New Delhi, Delhi
  • Maulana Azad Medical College — New Delhi, Delhi
  • Sanjay Gandhi Post Graduate Institute of Medical Sciences — Lucknow, Uttar Pradesh
  • Post Graduate Institute of Medical Education and Research (PGIMER) — Chandigarh, Chandigarh
  • Centre for DNA Fingerprinting & Diagnostics with Nizam’s Institute of Medical Sciences — Hyderabad, Telangana
  • King Edward Memorial Hospital — Mumbai, Maharashtra
  • Institute of Post-Graduate Medical Education and Research (IPGMER) — Kolkata, West Bengal
  • Centre for Human Genetics with Indira Gandhi Hospital — Bengaluru, Karnataka
  • Institute of Child Health and Hospital for Children (ICH & HC) — Chennai, Tamil Nadu
  • All India Institute of Medical Sciences (AIIMS) — Jodhpur, Rajasthan
  • Sree Avittam Thirunal Hospital (SAT), Government Medical College — Thiruvananthapuram, Kerala
  • All India Institute of Medical Sciences (AIIMS) — Bhopal, Madhya Pradesh
  • Regional Institute of Medical Sciences (RIMS) — Imphal, Manipur
  • All India Institute of Medical Sciences (AIIMS) — Patna, Bihar
  • Assam Medical College & Hospital — Dibrugarh, Assam

Voluntary contributions / crowdfunding (separate from CoE funding): https://rarediseases.mohfw.gov.in/

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("Hyperammonemia due to N-acetylglutamate synthase deficiency" OR "NAGS deficiency") OR (MESH:"N-acetyl glutamate synthetase deficiency") OR ("NAGS" OR "NAGS syndrome" OR "NAGS-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: N-acetyl glutamate synthetase deficiency

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Hyperammonemia due to N-acetylglutamate synthase deficiency" OR "NAGS deficiency" OR "N-acetyl glutamate synthetase deficiency"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 1 interventional · 3 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase, mesh; with hits: phrase, mesh

Run this search on ClinicalTrials.gov

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • No synonyms dropped by stoplist
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (3442) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T02:19:38.691Z