ORPHA:440427
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency
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
50
52th percentile
Trials
2
Interventional, condition-specific
Researchers
395
Distinct authors in sample
Gene link
MARS1
Strong
Readiness
3/6
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.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0014206
- OMIM:615486
- UMLS:C4225400
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.”
3/6 stages with a signal
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Strong — MARS1
- LiteraturePresent
50 matched papers (46 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- 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 (MARS1).
GenCC classification: Strong.
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?
50
50 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=5449) is 41.
50 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).
46 in the last 10 years · high confidence · 52th percentile (publications denominator)
Phrase hits: 50 · MeSH hits: 0
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.
- 01Andonovic 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 - 02Hadchouel 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 - 03Mark PB3 papers · 2025
Department of Nephrology, Queen Elizabeth University Hospital, United Kingdom.
Papers in Europe PMC - 04Puxty 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 - 05Staufner 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 - 06Traynor JP3 papers · 2025
Department of Nephrology, Queen Elizabeth University Hospital, United Kingdom.
Papers in Europe PMC - 07Antonellis 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 - 08Caligiuri G2 papers · 2021
Istituto di Genetica Molecolare 'Luigi Luca Cavalli-Sforza' (IGM) CNR, Via Abbiategrasso 207, Pavia 27100, Italy.
Papers in Europe PMC - 09Griese M2 papers · 2022
German Center for Lung Research (DZL), Hannover, Germany.
Papers in Europe PMC - 10Huang J2 papers · 2023
BGI-Wuhan Clinical Laboratory, BGI-Shenzhen, 430074, Wuhan, China.
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. 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 27 July 2026
2 interventional trials — more than 73% of diseases in the trials denominator have none at all (5114 of 7003; this disease is at the 82.4th percentile).
high confidence · 82.4th 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.
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
- NCT05761899·RECRUITING·Safety and Efficacy of PMT Therapy of hPAP
Conditions: Hereditary Pulmonary Alveolar Proteinosis·Matched via name phrase
- NCT06431776·RECRUITING·Inhaled Molgramostim in Pediatric Participants With Autoimmune Pulmonary Alveolar Proteinosis (aPAP).
Conditions: Autoimmune Pulmonary Alveolar Proteinosis·Matched via name phrase
- NCT06989333·NOT YET RECRUITING·Local Spraying of GM-CSF Via Bronchoscopy in the Treatment of Autoimmune Pulmonary Alveolar Proteinosis
Conditions: Pulmonary Alveolar Proteinosis·Matched via name phrase
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 2026-07-26This 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"
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" OR "MARS1"
Recall-expansion terms: MARS1
Interventional trials matched via: phrase, recall-expansion (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.
Parent-category trials query:
"pulmonary alveolar proteinosis"
Query health: ok — strategies attempted: phrase, recall-expansion; with hits: phrase, recall-expansion
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 2026-07-27T16:21:53.310Z