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ORPHA:2102

GTP cyclohydrolase I deficiency

low confidenceSubtype of disorder

Also known as: GTPCH deficiency · Hyperphenylalaninemia due to GTP cyclohydrolase deficiency

Publications

4,141

Trials

1

Interventional, condition-specific

Researchers

655

Distinct authors in sample

Gene link

GCH1

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

GTP-cyclohydrolase I deficiency, an genetic disorder, is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.

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 (2)

hyperphenylalaninemia due to GTP cyclohydrolase deficiency · hyperphenylalaninemia, Bh4-deficient, type B

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 — GCH1

  2. LiteraturePresent

    4,141 matched papers (3,144 in last 10 years) Source

  3. Phenotype characterisedPresent

    26 HPO annotations (e.g. Hyperkinetic movements; Intellectual disability; Elevated urinary sulfatide level) Source

  4. Animal modelPresent

    1 genotype model (Mus musculus) Source

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. Interventional trialPresent

    1 matched on ClinicalTrials.gov

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 (GCH1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

26

Associated phenotypes · MONDO:0100186

  • Hyperkinetic movements
  • Intellectual disability
  • Elevated urinary sulfatide level
  • Dysphagia
  • Progressive neurologic deterioration

Showing 5 of 26 — open Monarch for the full list.

Animal models (Monarch / Alliance)

1

Model associations linked to this Mondo ID

Monarch fetch 2026-07-29

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)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

4,141

4,141 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.

4,141 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).

3,144 in the last 10 years · low confidence

Phrase hits: 117 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

655

Distinct author names in 117 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
    Blau N21 papers · 2026

    University Children's Hospital, Dietmar-Hoppe Metabolic Centre, Heidelberg, Germany.

    Papers in Europe PMC
  2. 02
    Opladen T9 papers · 2026

    Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany.

    Papers in Europe PMC
  3. 03
    Thöny B9 papers · 2021

    Division of Clinical Chemistry and Biochemistry, Laboratory of Molecular Genetic Investigation, University Children's Hospital Zürich, Zürich, Switzerland.

    Papers in Europe PMC
  4. 04
    Hoffmann GF7 papers · 2026

    Department of Pediatrics, University of Heidelberg, Heidelberg, Germany. georg_hoffmann@med.uni-heidelberg.de

    Papers in Europe PMC
  5. 05
    Nagatsu T7 papers · 2024

    Nagoya University Research Institute of Environmental Medicine, Nagoya, Japan . ; Fujita Health University School of Medicine, Toyoake, Aichi, Japan . ; Visiting Professor and Professor Emeritus.

    Papers in Europe PMC
  6. 06
    Burlina A5 papers · 2021

    Division of Inherited Metabolic Diseases, Department of Paediatrics, University Hospital of Padova, Padova, Italy.

    Papers in Europe PMC
  7. 07
    Niederwieser A5 papers · 1986
    Papers in Europe PMC
  8. 08
    Channon KM4 papers · 2017

    BHF Centre of Research Excellence, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. Electronic address: keith.channon@cardiov.ox.ac.uk.

    Papers in Europe PMC
  9. 09
    Crabtree MJ4 papers · 2017

    BHF Centre of Research Excellence, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom.

    Papers in Europe PMC
  10. 10
    Leuzzi V4 papers · 2024

    Department of Paediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Via dei Sabelli 108, 00185, Rome, Italy.

    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; none in our sample are currently recruiting.

Data as of 11 September 2026 · last trial check 28 July 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.

No currently recruiting studies in the matched set. Open the same search on ClinicalTrials.gov.

Observational and natural-history studies

1 observational study matches 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.

None of the matched observational studies is currently listed as 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 1 · after dedupe 1 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 1 · dropped 0 · fetched 2026-07-29

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).

Uncertain / not reviewed (1)

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 GTP cyclohydrolase I deficiency — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

Likely covered — the policy lists Non-PKU hyperphenylalaninemia as a category (Group 2), and this condition is a form of it. Confirm eligibility with a Centre of Excellence.

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.

("GTP cyclohydrolase I deficiency" OR "GTPCH deficiency" OR "Hyperphenylalaninemia due to GTP cyclohydrolase deficiency" OR "hyperphenylalaninemia, Bh4-deficient, type B") OR ("GCH1" OR "GCH1 syndrome" OR "GCH1-related" OR "GTP syndrome" OR "GTP-related")

Run this search on Europe PMC

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

"GTP cyclohydrolase I deficiency" OR "GTPCH deficiency" OR "Hyperphenylalaninemia due to GTP cyclohydrolase deficiency" OR "hyperphenylalaninemia, Bh4-deficient, type B"

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 · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

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

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 (4141) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T19:06:54.198Z