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ORPHA:440427

Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency

low confidenceDisorder

Also known as: Hereditary pulmonary alveolar proteinosis with hepatic involvement · Interstitial lung and liver disease · PAP, Reunion island type · Pulmonary alveolar proteinosis, Reunion island type

Publications

538

Trials

1

Interventional, condition-specific

Researchers

395

Distinct authors in sample

Gene link

MARS1

Strong

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic interstitial lung disease characterized by accumulation of lipoproteins in the pulmonary alveoli leading to restrictive lung disease and respiratory failure. Patients present with dyspnea, tachypnea, cough, , and digital clubbing. Liver disease have been described in some cases including , steatosis, fibrosis or cirrhosis.

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 (3)

hereditary pulmonary alveolar proteinosis with hepatic involvement · interstitial lung and liver disease · pulmonary alveolar proteinosis, Reunion island type

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

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Strong — MARS1

  2. LiteraturePresent

    538 matched papers (492 in last 10 years) Source

  3. Phenotype characterisedPresent

    27 HPO annotations (e.g. Hepatic steatosis; Cholestasis; Aminoaciduria) 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 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 (MARS1).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

27

Associated phenotypes · MONDO:0014206

  • Hepatic steatosis
  • Cholestasis
  • Aminoaciduria
  • Hypotonia
  • Cough

Showing 5 of 27 — 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?

538

538 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.

538 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).

492 in the last 10 years · low confidence

Phrase hits: 50 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

395

Distinct author names in 50 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
    Andonovic M3 papers · 2025

    Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom.

    Papers in Europe PMC
  2. 02
    Hadchouel A3 papers · 2023

    AP-HP, Hôpital Necker-Enfants Malades, Service de Pneumologie Pédiatrique, Centre de Référence pour les Maladies Respiratoires Rares de l'Enfant, Paris, France alice.hadchouel-duverge@aphp.fr.

    Papers in Europe PMC
  3. 03
    Mark PB3 papers · 2025

    Department of Nephrology, Queen Elizabeth University Hospital, United Kingdom.

    Papers in Europe PMC
  4. 04
    Puxty KA3 papers · 2025

    Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom.

    Papers in Europe PMC
  5. 05
    Staufner C3 papers · 2025

    Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany. Electronic address: christian.staufner@med.uni-heidelberg.de.

    Papers in Europe PMC
  6. 06
    Traynor JP3 papers · 2025

    Department of Nephrology, Queen Elizabeth University Hospital, United Kingdom.

    Papers in Europe PMC
  7. 07
    Antonellis A2 papers · 2018

    Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, United States; Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI, United States. Electronic address: antonell@umich.edu.

    Papers in Europe PMC
  8. 08
    Caligiuri G2 papers · 2021

    Istituto di Genetica Molecolare 'Luigi Luca Cavalli-Sforza' (IGM) CNR, Via Abbiategrasso 207, Pavia 27100, Italy.

    Papers in Europe PMC
  9. 09
    Griese M2 papers · 2022

    German Center for Lung Research (DZL), Hannover, Germany.

    Papers in Europe PMC
  10. 10
    Huang J2 papers · 2023

    BGI-Wuhan Clinical Laboratory, BGI-Shenzhen, 430074, Wuhan, China.

    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. 22 trials are registered for pulmonary alveolar proteinosis, the broader category — shown separately because they may or may not enrol this specific subtype.

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.

Broader category: pulmonary alveolar proteinosis

22

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.

Recruiting under the broader category

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 40 · after dedupe 40 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 40 · 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).

Uncertain / not reviewed (40)

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 Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency — 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.

("Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency" OR "Hereditary pulmonary alveolar proteinosis with hepatic involvement" OR "Interstitial lung and liver disease" OR "PAP, Reunion island type" OR "Pulmonary alveolar proteinosis, Reunion island type") OR ("MARS1" OR "MARS1 syndrome" OR "MARS1-related")

Run this search on Europe PMC

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

"Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency" OR "Hereditary pulmonary alveolar proteinosis with hepatic involvement" OR "Interstitial lung and liver disease" OR "PAP, Reunion island type" OR "Pulmonary alveolar proteinosis, Reunion island type"

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

Parent-category trials query:

"pulmonary alveolar proteinosis"

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

Ingested 2026-07-27T16:21:53.310Z