ORPHA:226
Dihydropteridine reductase deficiency
Also known as: Hyperphenylalaninemia due to dihydropteridine reductase deficiency · PKU type 2 · Phenylketonuria type 2
Publications
2,984
Trials
0
Interventional, condition-specific
Researchers
1,366
Distinct authors in sample
Gene link
QDPR
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare form of hyperphenylalaninemia due to tetrahydropterin (BH4) recycling deficiency, leading to central dopamine and serotonin deficiency, clinically characterized by -onset neurological disease of variable severity ranging from mild forms with minor neurological development to severe forms with , , complex movement disorder dominated by dystonia or dystonia parkinsonism. Some patients may present refractory neurological symptoms like a degree of , and brain abnormalities.
How rare: How common this is has not been clearly measured.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0009862
- OMIM:261630
- UMLS:C0268465
- NCIT:C138173
Additional Mondo synonyms (7)
6,7-dihydropteridine reductase activity disease · dihydropteridine reductase deficiency · disorder of 6,7-dihydropteridine reductase activity · hyperphenylalaninemia due to dihydropteridine reductase deficiency · hyperphenylalaninemia, BH4-deficient C · hyperphenylalaninemia, Bh4-deficient, type C · phenylketonuria type 2
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.”
3/6 stages with a signal
No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.
- Gene identifiedPresent
Definitive — QDPR
- LiteraturePresent
2,984 matched papers (1,493 in last 10 years) Source
- Phenotype characterisedPresent
22 HPO annotations (e.g. Dystonia; Recurrent fever; Tremor) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialNot found
No matched interventional trial under our ClinicalTrials.gov rules
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 (QDPR).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
22
Associated phenotypes · MONDO:0009862
- Dystonia
- Recurrent fever
- Tremor
- Myoclonus
- Hypertonia
Showing 5 of 22 — 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 2026-07-29
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?
2,984
2,984 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.
2,984 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).
1,493 in the last 10 years · low confidence
Phrase hits: 894 · MeSH hits: 0
Who's working on it?
1,366
Distinct author names in 200 sampled papers — named people below.
Who's working on it?
No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.
- 01Liu J7 papers · 2026
Department of Emergency, First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Papers in Europe PMC - 02Leuzzi V6 papers · 2025
Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza, University of Rome, Rome, Italy.
Papers in Europe PMC - 03Mastrangelo M6 papers · 2025
Child Neurology and Psychiatry Unit, Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy.
Papers in Europe PMC - 04Opladen T6 papers · 2021
Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany.
Papers in Europe PMC - 05Ichinose H5 papers · 2026
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
Papers in Europe PMC - 06Wang X5 papers · 2026
Clinical Neuroscience Research Center, Departments of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
Papers in Europe PMC - 07Blau N4 papers · 2020
Division of Metabolism, University Children's Hospital Zurich, Zurich, Switzerland
Papers in Europe PMC - 08Cortès-Saladelafont E4 papers · 2021
Inborn Errors of Metabolism Unit, Department of Neurology, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain.
Papers in Europe PMC - 09Friedman J4 papers · 2021
UCSD Departments of Neuroscience and Pediatrics; Rady Children's Hospital Division of Neurology, Rady Children's Institute for Genomic Medicine, San Diego, California, USA.
Papers in Europe PMC - 10García-Cazorla A4 papers · 2021
Inborn Errors of Metabolism Unit, Department of Neurology, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
0
interventional trials for this specific condition
No interventional trial testing a treatment matched this specific condition name. 1 observational study did — shown below because natural-history and cohort work can be an important step toward a trial.
Data as of 11 September 2026 · last trial check 11 September 2026
No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.
low confidence · 38.6th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.
See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.
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.
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 5 · after dedupe 4 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 4 · 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 (4)
- isrctn·ISRCTN79102999·No longer recruiting·A Phase III study of sepiapterin versus sapropterin in participants with phenylketonuria ≥2 years of age
skipped — LLM skipped (--skip-llm)
- isrctn·ISRCTN12192375·Recruiting·Longitudinal physiological changes in inherited metabolic disorders
skipped — LLM skipped (--skip-llm)
- isrctn·ISRCTN38904316·Stopped·Acceptability and tolerability of a new phe-free protein substitute for the dietary management of patients with phenylketonuria, aged ≥16 years
skipped — LLM skipped (--skip-llm)
- isrctn·ISRCTN17091496·No longer recruiting·Casein+ study: Dietary strategies to augment post-prandial muscle protein accretion
skipped — LLM skipped (--skip-llm)
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 Dihydropteridine reductase deficiency — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26Likely 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.
("Dihydropteridine reductase deficiency" OR "Hyperphenylalaninemia due to dihydropteridine reductase deficiency" OR "PKU type 2" OR "Phenylketonuria type 2" OR "6,7-dihydropteridine reductase activity disease" OR "disorder of 6,7-dihydropteridine reductase activity" OR "hyperphenylalaninemia, BH4-deficient C" OR "hyperphenylalaninemia, Bh4-deficient, type C") OR ("QDPR" OR "QDPR syndrome" OR "QDPR-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Dihydropteridine reductase deficiency" OR "Hyperphenylalaninemia due to dihydropteridine reductase deficiency" OR "PKU type 2" OR "Phenylketonuria type 2" OR "6,7-dihydropteridine reductase activity disease" OR "disorder of 6,7-dihydropteridine reductase activity" OR "hyperphenylalaninemia, BH4-deficient C" OR "hyperphenylalaninemia, Bh4-deficient, type C"
Study-type breakdown: 0 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 (2984) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity
Ingested 2026-07-26T12:58:12.609Z