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ORPHA:163690

Hypotonia-cystinuria syndrome

low confidenceDisorder

Also known as: HCS

Publications

5,117

Trials

2

Interventional, condition-specific

Researchers

528

Distinct authors in sample

Gene link

PREPL

Strong

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic disorder of amino acid absorption and transport, characterized by generalized at birth, / (followed by hyperphagia and rapid weight gain in late childhood), cystinuria type 1, nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism. features mainly include dolichocephaly and ptosis. Nephrolithiasis occurs at variable ages.

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 (4)

cystinuria with mitochondrial disease · hypotonia-cystinuria syndrome · hypotonia-cystinuria syndrome type 1 · hypotonia-cystinuria type 1 syndrome

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

    Strong — PREPL

  2. LiteraturePresent

    5,117 matched papers (2,646 in last 10 years) Source

  3. Phenotype characterisedPresent

    49 HPO annotations (e.g. Ptosis; Growth delay; Decreased fetal movement) Source

  4. Animal modelPresent

    2 genotype models (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

    2 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 (PREPL).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

49

Associated phenotypes · MONDO:0011669

  • Ptosis
  • Growth delay
  • Decreased fetal movement
  • Cystinuria
  • Dolichocephaly

Showing 5 of 49 — open Monarch for the full list.

Animal models (Monarch / Alliance)

2

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

1

Drugs / clinical candidates · MONDO_0011669

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

5,117

5,117 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

5,117 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).

2,646 in the last 10 years · low confidence

Phrase hits: 76 · MeSH hits: 2

Open Europe PMC search

Who's working on it?

528

Distinct author names in 76 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
    Meulemans S10 papers · 2024

    Laboratory of Biochemical Neuroendocrinology, Department of Human Genetics, University of Leuven, Leuven, Belgium.

    Papers in Europe PMC
  2. 02
    Creemers JW9 papers · 2024

    Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, ON1 Herestraat 49 - b 607, 3000, Belgium

    Papers in Europe PMC
  3. 03
    Jaeken J8 papers · 2012

    Department of Paediatrics, University Hospitals Leuven, Belgium.

    Papers in Europe PMC
  4. 04
    Martens K6 papers · 2009

    Laboratory of Biochemical Neuroendocrinology, Department for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium.

    Papers in Europe PMC
  5. 05
    Matthijs G6 papers · 2009
    Papers in Europe PMC
  6. 06
    Creemers J5 papers · 2014

    Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven, Belgium.

    Papers in Europe PMC
  7. 07
    Régal L5 papers · 2021

    Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven, Belgium.

    Papers in Europe PMC
  8. 08
    Eggermann T4 papers · 2018

    Institut für Humangenetik, RWTH Aachen, Aachen, Germany. teggermann@ukaachen.de

    Papers in Europe PMC
  9. 09
    Bhalla K3 papers · 2024

    Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Leuven, Belgium.

    Papers in Europe PMC
  10. 10
    Cravatt BF3 papers · 2021

    The Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

2

interventional trials for this specific condition

2 interventional trials matched this specific condition name; none in our sample are currently recruiting.

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

2 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 84.5th percentile).

low confidence · 84.5th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

2 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.

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 2026-07-30

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 Hypotonia-cystinuria syndrome — 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.

("Hypotonia-cystinuria syndrome" OR "cystinuria with mitochondrial disease" OR "hypotonia-cystinuria syndrome type 1" OR "hypotonia-cystinuria type 1 syndrome") OR (MESH:"Hypotonia-Cystinuria Syndrome") OR ("PREPL" OR "PREPL syndrome" OR "PREPL-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Hypotonia-Cystinuria Syndrome

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

"Hypotonia-cystinuria syndrome" OR "cystinuria with mitochondrial disease" OR "hypotonia-cystinuria syndrome type 1" OR "hypotonia-cystinuria type 1 syndrome"

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

Study-type breakdown: 2 interventional · 0 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

Synonyms dropped by stoplist: HCS

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (5117) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T08:10:54.635Z