Interstitial lung disease: a 2-year-old child with ABCA3 deficiency treated by CFTR potentiators
Bibliographic record
Abstract
Background: Pathogenic variants in ATP biding cassette A3 (ABCA3) gene can cause chronic interstitial lung diseases (ILD). As a lipid transporter involved in surfactant homeostasis, ABCA3 shares similarities with the cystic fibrosis transmembrane conductance regulator (CFTR). In vitro studies suggest CFTR potentiators may restore function of ABCA3 variants. We report a compassionate trial of CFTR modulators in a 2-year-old with ABCA3 deficiency. Method: Trio whole-genome rapid sequencing identified ABCA3 compound heterozygous variations supporting a diagnosis of ABCA3 deficiency (PRAGMatIQ study, Québec). After independent expert panel review (Respifil, France), a trial of CFTR modulation with elaxacaftor-tezacaftor-ivacaftor (ETI) was started (Trikafta, Vertex Pharmaceuticals). The SpO2/FiO2 (S/F) ratio was recorded for primary outcome. Results: Patient presented with failure to thrive, development delay, and progressive respiratory distress requiring PICU admission for continuous positive airway pressure with FiO2 40%-70%. Chest CT showed diffuse ground glass opacities, ILD workup was negative. Despite 10 weeks of standard treatment, he remained with hypoxic respiratory failure (median S/F ratio 380, IQR 338-411). Eight days after ETI initiation, respiratory support was gradually weaned as S/F ratio normalized (median 463; IQR 458-467; P<0.001). He was transferred to the ward at 17 days and discharged after 9 weeks. Conclusion: While confounding factors cannot be excluded, marked improvement with ETI may indicate ABCA3 functional rescue by CFTR potentiators. Residual gene function is likely given heterozygosity for a non-canonical splicing variant and the late clinical presentation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.005 | 0.004 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".