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ORPHA:79101

Hyperprolinemia type 2

low confidenceDisorder

Also known as: Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency

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

Publications

1,389

Trials

0

Interventional, condition-specific

Researchers

105

Distinct authors in sample

Gene link

ALDH4A1

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

Hyperprolinemia type 2 is an proline metabolism disorder due to pyroline-5-carboxylate dehydrogenase deficiency. The condition is often benign but clinical signs may include , intellectual deficit and mild .

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)

1-pyrroline-5-carboxylate dehydrogenase activity disease · ALDH4A1 hyperprolinemia · delta-1-pyrroline-5-carboxylate dehydrogenase deficiency · delta1-pyrroline-5-carboxylate dehydrogenase deficiency · disorder of 1-pyrroline-5-carboxylate dehydrogenase activity · hyperprolinemia caused by mutation in ALDH4A1 · hyperprolinemia 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.”

4/6 stages with a signal

No specific-condition interventional trial, but broader-category trials exist — discuss eligibility with a clinician.

  1. Gene identifiedPresent

    Definitive — ALDH4A1

  2. LiteraturePresent

    1,389 matched papers (975 in last 10 years) Source

  3. Phenotype characterisedPresent

    60 HPO annotations (e.g. Atypical behavior; Abnormal cerebrospinal fluid morphology; Hydroxyprolinuria) Source

  4. Animal modelNot found

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

  5. Orphan designationNot found

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

  6. Interventional trialPartial

    None under the specific name; 1 for broader category hyperprolinemia

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 (ALDH4A1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

60

Associated phenotypes · MONDO:0009401

  • Atypical behavior
  • Abnormal cerebrospinal fluid morphology
  • Hydroxyprolinuria
  • Reduced circulating vitamin B6 circulating
  • Chronic fatigue

Showing 5 of 60 — 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)

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?

1,389

1,389 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.

1,389 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).

975 in the last 10 years · low confidence

Phrase hits: 16 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

105

Distinct author names in 16 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
    Ferreira CR2 papers · 2019

    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; Rare Disease Institute, Children's National Health System, Washington, DC, United States.

    Papers in Europe PMC
  2. 02
    van Karnebeek CDM2 papers · 2019

    Departments of Pediatrics and Clinical Genetics, Amsterdam University Medical Centers, Amsterdam, The Netherlands; Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada. Electronic address: c.d.vankarnebeek@amstedarmumc.nl.

    Papers in Europe PMC
  3. 03
    Akar HT1 paper · 2023

    Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism, Turkey. Electronic address: halil.tuna.akar@hacettepe.edu.tr.

    Papers in Europe PMC
  4. 04
    Attie AD1 paper · 2019

    Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.

    Papers in Europe PMC
  5. 05
    Ayzenberg I1 paper · 2019

    Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany.

    Papers in Europe PMC
  6. 06
    Bak M1 paper · 2019

    Department of Clinical Genetics Copenhagen University Hospital Copenhagen Denmark.

    Papers in Europe PMC
  7. 07
    Barbaro M1 paper · 2019

    Centre for Inherited Metabolic Diseases Karolinska University Hospital Stockholm Sweden.

    Papers in Europe PMC
  8. 08
    Barth M1 paper · 2021

    Service de génétique médicale, CHU d'Angers, Angers, France.

    Papers in Europe PMC
  9. 09
    Barthez MA1 paper · 2021

    Service de neuropédiatrie, CHU de Tours, Tours, France.

    Papers in Europe PMC
  10. 10
    Blau N1 paper · 2018

    Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany.

    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 on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present). 1 trial are registered for hyperprolinemia, the broader category — shown separately because they may or may not enrol this specific subtype.

Data as of 9 September 2026 · last trial check 9 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.

1 interventional trial matched hyperprolinemia, the broader category — listed below. Those studies are not counted in the condition-specific total.

Broader category: hyperprolinemia

1

Interventional trials for the parent category, exclusive of NCT IDs already counted above. Eligibility for this subtype is not guaranteed.

Worth raising with a clinician. How we count trials.

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 Hyperprolinemia type 2 — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

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.

("Hyperprolinemia type 2" OR "Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency" OR "1-pyrroline-5-carboxylate dehydrogenase activity disease" OR "ALDH4A1 hyperprolinemia" OR "delta1-pyrroline-5-carboxylate dehydrogenase deficiency" OR "disorder of 1-pyrroline-5-carboxylate dehydrogenase activity" OR "hyperprolinemia caused by mutation in ALDH4A1") OR (MESH:"Hyperprolinemia type 2") OR ("ALDH4A1" OR "ALDH4A1 syndrome" OR "ALDH4A1-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Hyperprolinemia type 2

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

"Hyperprolinemia type 2" OR "Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency" OR "1-pyrroline-5-carboxylate dehydrogenase activity disease" OR "ALDH4A1 hyperprolinemia" OR "delta1-pyrroline-5-carboxylate dehydrogenase deficiency" OR "disorder of 1-pyrroline-5-carboxylate dehydrogenase activity" OR "hyperprolinemia caused by mutation in ALDH4A1"

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

Parent-category trials query:

"hyperprolinemia"

Query health: suspect — strategies attempted: phrase, mesh; 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 (1389) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-26T01:59:57.354Z