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ORPHA:226

Dihydropteridine reductase deficiency

high confidenceSubtype of disorder

Also known as: Hyperphenylalaninemia due to dihydropteridine reductase deficiency · PKU type 2 · Phenylketonuria type 2

Query health: suspect — Only one of 2 strategies returned hits (phrase).

Publications

894

89th percentile

Trials

0

Interventional, condition-specific

Researchers

1,286

Distinct authors in sample

Gene link

QDPR

Definitive

Readiness

2/6

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.

Orphanet entry

Cross-references

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

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.”

2/6 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.

  1. Gene identifiedPresent

    Definitive — QDPR

  2. LiteraturePresent

    894 matched papers (438 in last 10 years) Source

  3. Phenotype characterisedNot checked

    Not yet enriched from Monarch / HPO

  4. Animal modelNot checked

    Not yet enriched from Monarch / Alliance

  5. Orphan designationNot checked

    FDA/EMA orphan-drug designation not enriched yet

  6. 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)

Not enriched in this build — Monarch phenotype joins were not run for this record.

Animal models (Monarch / Alliance)

Not enriched in this build.

Literature

Is anyone studying this?

894

894 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=5449) is 41.

894 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).

438 in the last 10 years · high confidence · 89th percentile (publications denominator)

Phrase hits: 894 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,286

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.

  1. 01
    Leuzzi V6 papers · 2025

    Department of Human Neuroscience, Unit of Child Neurology and Psychiatry, Università degli Studi di Roma La Sapienza, Rome, Italy.

    Papers in Europe PMC
  2. 02
    Mastrangelo M5 papers · 2025

    Department of Human Neuroscience, Unit of Child Neurology and Psychiatry, Università degli Studi di Roma La Sapienza, Rome, Italy.

    Papers in Europe PMC
  3. 03
    Opladen T5 papers · 2021

    University Children's Hospital Heidelberg, Division of Child Neurology and Metabolic Disorders, Heidelberg, Germany. Thomas.Opladen@med.uni-heidelberg.de.

    Papers in Europe PMC
  4. 04
    Porta F5 papers · 2021

    Department of Pediatrics, University of Torino, Italy. porta.franc@gmail.com

    Papers in Europe PMC
  5. 05
    Blau N4 papers · 2020

    University Children's Hospital, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany. Electronic address: nenad.blau@med.uni-heidelberg.de.

    Papers in Europe PMC
  6. 06
    Cortès-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
  7. 07
    Friedman 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, CA, USA.

    Papers in Europe PMC
  8. 08
    García-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
  9. 09
    Hoffmann GF4 papers · 2021

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

    Papers in Europe PMC
  10. 10
    Honzík T4 papers · 2021

    Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

    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 27 July 2026

No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.

high confidence · 36.5th 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.

Open the complete matched search on ClinicalTrials.gov

Where to find support

We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:

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.

"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"

Run this search on Europe PMC

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" OR "QDPR"

Recall-expansion terms: QDPR

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

Query health: suspect — strategies attempted: phrase, recall-expansion; 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

Ingested 2026-07-26T12:58:12.609Z