ABCA3-related interstitial lung disease beyond infancy

Li Y, Seidl E, Knoflach K, Gothe F, Forstner ME, Michel K, Pawlita I, Gesenhues F, Sattler F, Yang X, Kroener C, Reu-Hofer S, Ley-Zaporozhan J, Kammer B, Krueger-Stollfuss I, Dinkel J, Carlens J, Wetzke M, Moreno-Galdo A, Torrent-Vernetta A, Lange J, Krenke K, Rumman N, Mayell S, Sismanlar T, Aslan A, Regamey N, Proesmans M, Stehling F, Naehrlich L, Ayse K, Becker S, Koerner-Rettberg C, Plattner E, Manali ED, Papiris SA, Campo I, Kappler M, Schwerk N, Griese M (2023)

Publication Type: Journal article

Publication year: 2023


DOI: 10.1136/thorax-2022-219434


BackgroundThe majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year. MethodOver a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly. ResultsAt the end of the observation period, median age was 6.3 years (IQR: 2.8-11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss -1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, the ABCA3 sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function. ConclusionThe natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.

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How to cite


Li, Y., Seidl, E., Knoflach, K., Gothe, F., Forstner, M.E., Michel, K.,... Griese, M. (2023). ABCA3-related interstitial lung disease beyond infancy. Thorax.


Li, Yang, et al. "ABCA3-related interstitial lung disease beyond infancy." Thorax (2023).

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