Table 2. Clinical course and phenotype.
| Case | Sex, gestational age, birth weight, family history | Presentation and clinical course | HRCT imaging | Treatment and outcome | ProSP-C expression and amyloid staining | Ultrastructure |
|---|---|---|---|---|---|---|
| 1 | F; term; 3.30 Kg Parents and one sibling healthy | Dyspnea and failure to thrive at 1 m PICU from 3 m Lung biopsy 3 m | 3 m: ground glass opacities, upper lobes cysts, upper lobar emphysema, PTX | O2 from 1 m, MV from 3 m PS+HCQ from 3 m Death 6 m | AEC2 hyperplasia Granular proSP-C pattern with diffuse large aggregates Several amyloid deposits | Many large endosomes Very rare LBs with abnormal PL structure |
| 2 | M; term; 3.70 Kg Parents healthy, no siblings | Multiple bronchiolitis episodes 3–12 m Hypoxemia from 14 m PICU from 14 m Lung biopsy 18 m | 14 m: ground glass opacities, multifocal interstitial infiltrates | O2 from 14 m, MV from 15 m, tracheostomy 16 m PS+HCQ from 15 m Death 19 m | Marked AEC2 hyperplasia Granular proSP-C pattern with diffuse large aggregates No amyloid detected | Many large endosomes with some PL content Very rare immature LBs and MVBs |
| 3 | M; term; 3.00 Kg Healthy parents and sister | Bronchiolitis 5 m PICU 9–13m for respiratory failure, recurrent PTX Lung biopsy 15 m | 9 m: ground glass opacities, multiple cysts | O2 from 11 m, MV 9–11 m PS+HCQ from 13 m Alive on O2 at 48 m Listed for transplant | AEC2 hyperplasia Granular proSP-C pattern with diffuse large aggregates No amyloid detected | Many large endosomes with PL content Very rare LBs |
| 4 | F; term; 3.30 Kg 1 sibling, fatal respiratory failure 16 m | Chronic cough and dyspnea since 7 m PICU 18–19 m for hypoxemia and dyspnea | 10 m: diffuse ground glass opacities, honeycombing, multiple subpleural nodules. | O2 18–21 m HCQ from 21 m Alive on room air at 30 m | n/a | n/a |
| 5 | M, Term, 2.990 Kg Parents healthy, no siblings | Chronic cough, failure to thrive since 9 m Hospitalized 13–14 m for dyspnea and hypoxemia | 13 m: diffuse ground glass opacities | O2 13–19 m Steroids for 5 m at 13 m AZM 18 m, HCQ from 13 m Alive on room air at 21 m | n/a | (tracheal aspirate) Some large endosomes with PL content Rare MVBs |
| 6 | F; term; 3.03 Kg Parents healthy, no siblings | Hospitalized for bronchiolitis at 6 m Hospitalized 11–15 m for hypoxemia and PTX, lung biopsy at 14 m | 6 m: diffuse ground glass opacities, basal emphysema | O2 since 13 m, MV 6–7 m PS 11–12 m HCQ from 16 m Alive on O2 at 24 m | Marked AEC2 hyperplasia Some granular proSP-C pattern plus perinuclear aggregates Rare amyloid deposits | Numerous mitochondria, lysosomes and electron-dense deposits Several normal LBs Several MVBs |
| 7 | F; term; 3.00 Kg Parents healthy, no siblings | Pneumonia at 1 y, Several hospitalizations for LRTI in childhood; severe failure to thrive Hypoxemia at 26 y | 26 y: mild interstitial lung disease, diffuse tubular and varicose bronchiectasis, basal infiltrates | Intermittently on O2, never ventilated Multiple antibiotic and PS courses, bronchodilators Alive at 28 y on O2 | n/a | n/a |
| 8 | M; 28 w; 0.90 Kg Parents healthy, two triplet siblings with no CLD | Severe RDS at birth, 2 doses of surfactant, MV until 4w | 2 m: diffuse ground glass opacities, overexpansion, bronchial markings | O2 2–4 m, MV 1 m Steroids 1 m Alive on room air at 14 m | n/a | n/a |
Abbreviations: AEC2, alveolar epithelial type 2 cells; AZM, azithromycin; CLD, chronic lung disease; F, female; HCQ, hydroxychloroquine; HRCT, high-resolution computerized tomography; ILD, interstitial lung disease; LB, lamellar bodies; LRTI, lower respiratory tract infection; M, male; m, month; MV, mechanical ventilation; MVB, multivesicular bodies; O2, supplemental oxygen; PICU, pediatric intensive care unit; PL, phospholipids; PS, pulse steroids; PTX, pneumothorax; RDS, respiratory distress syndrome; w, weeks; y, years.