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ORPHA:264675

Hereditary pulmonary alveolar proteinosis

low confidenceDisorder

Also known as: Congenital PAP · Congenital pulmonary alveolar proteinosis

Publications

3,740

Trials

2

Interventional, condition-specific

Researchers

1,137

Distinct authors in sample

Gene link

ACADL

Limited

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic, interstitial lung disease due to mutations in the CSF2R (colony-stimulating factor 2 receptor) alpha or beta subunits and characterized by alveolar accumulation of pulmonary surfactant, presenting a highly variable clinical presentation, ranging from asymptomatic to severe respiratory failure. Characteristic lung biopsy findings include periodic acid-Schiff-positive, granular eosinophilic material, enlarged foamy alveolar macrophages, and well-preserved alveolar walls. The Granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor function is impaired but GM-CSF receptor autoantibodies are absent.

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 (5)

congenital PAP · congenital pulmonary alveolar proteinosis · hereditary pulmonary alveolar proteinosis · inborn error of pulmonary surfactant metabolism · inborn error of surfactant metabolism

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

    Limited — ACADL

  2. LiteraturePresent

    3,740 matched papers (2,510 in last 10 years) Source

  3. Phenotype characterisedPresent

    139 HPO annotations (e.g. Intraalveolar phospholipid accumulation; Ground-glass opacification; Anti-granulocyte-macrophage colony stimulating factor antibody positivity) 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

    2 matched on ClinicalTrials.gov (1 recruiting in sample)

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?

Possibly — only limited evidence so far for ACADL.

GenCC classification: Limited.

Phenotypes (Monarch / HPO)

139

Associated phenotypes · MONDO:0012580

  • Intraalveolar phospholipid accumulation
  • Ground-glass opacification
  • Anti-granulocyte-macrophage colony stimulating factor antibody positivity
  • Respiratory insufficiency

Showing 4 of 139 — 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?

3,740

3,740 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.

3,740 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).

2,510 in the last 10 years · low confidence

Phrase hits: 396 · MeSH hits: 8

Open Europe PMC search

Who's working on it?

1,137

Distinct author names in 200 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
    Trapnell BC18 papers · 2024

    Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Bruce.Trapnell@cchmc.org.

    Papers in Europe PMC
  2. 02
    Lachmann N16 papers · 2026

    Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.

    Papers in Europe PMC
  3. 03
    Suzuki T14 papers · 2024

    Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, MLC7029, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address: Takuji.Suzuki@cchmc.org.

    Papers in Europe PMC
  4. 04
    McCarthy C12 papers · 2025

    Department of Medicine, St. Vincent's University Hospital and University College Dublin, Dublin, Ireland.

    Papers in Europe PMC
  5. 05
    Moritz T11 papers · 2020

    RG Reprograming and Gene Therapy, Institute of Experimental Hematology, Hannover Medical School, Carl Neuberg-Str. 1, 30625 Hannover, Germany.

    Papers in Europe PMC
  6. 06
    Nakata K10 papers · 2026

    Bioscience Medical Research Center, Niigata University, Niigata, Japan.

    Papers in Europe PMC
  7. 07
    Chalk C9 papers · 2024

    Translational Pulmonary Science Center, Children's Hospital Medical Center, Cincinnati, OH, USA.

    Papers in Europe PMC
  8. 08
    Ackermann M8 papers · 2020

    Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.

    Papers in Europe PMC
  9. 09
    Carey BC8 papers · 2024

    Translational Pulmonary Science Center, Children's Hospital Medical Center, Cincinnati, OH, USA.

    Papers in Europe PMC
  10. 10
    Hansen G8 papers · 2026

    Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; Department of Pediatric Pneumology, Allergology and Neonatology, MHH, Hannover, Germany.

    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; 1 currently recruiting in our sample. 20 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

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.

Broader category: pulmonary alveolar proteinosis

20

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 2 · after dedupe 2 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 2 · 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 (2)

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 Hereditary pulmonary alveolar proteinosis — 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.

("Hereditary pulmonary alveolar proteinosis" OR "Congenital PAP" OR "Congenital pulmonary alveolar proteinosis" OR "inborn error of pulmonary surfactant metabolism" OR "inborn error of the pulmonary surfactant metabolism" OR "inborn error of surfactant metabolism" OR "inborn error of the surfactant metabolism") OR (MESH:"Pulmonary alveolar proteinosis, congenital") OR ("ACADL" OR "ACADL syndrome" OR "ACADL-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Pulmonary alveolar proteinosis, congenital

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

"Hereditary pulmonary alveolar proteinosis" OR "Congenital PAP" OR "Congenital pulmonary alveolar proteinosis" OR "inborn error of pulmonary surfactant metabolism" OR "inborn error of the pulmonary surfactant metabolism" OR "inborn error of surfactant metabolism" OR "inborn error of the surfactant metabolism" OR "Pulmonary alveolar proteinosis, congenital"

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: 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, mesh; with hits: phrase, mesh

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 (3740) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T11:25:24.529Z