Manon Fleury, Céline Delestrain, Alice Hadchouel, Julie Mazenq, Myriam Benhamida, Anne‐Sophie Bernard, Raphaël Borie, Jacques Brouard, Harriet Corvol, Pierrick Cros, Christophe Delacourt, Tifenn Desroziers, Jean‐Christophe Dubus, Carole Egron, Ralph Epaud, Michael Fayon, Aude Forgeron, Lisa Giovannini‐Chami, Christophe Marguet, Alexandra Masson‐Rouchaud, Hortense Petat, Marie‐Catherine Renoux, Léa Roditis, Caroline Thumerelle, Clémentine Vigier, Aurore Coulomb L’Herminé, Hubert Ducou le Pointe, Pascale Fanen, Camille Fletcher, Chiara Sileo, Laureline Berteloot, Camille Louvrier, Alix de Becdelièvre, Marie Legendre, Nadia Nathan
Armand Trousseau Hospital and Sorbonne Université. Centre Hospitalier Intercommunal de Créteil and Reference Centre for Rare Lung Diseases. Université Paris Est Créteil. Necker Enfants Malades Hospital, AP-HP and Université de Paris. Aix-Marseille University. CHU Nantes. Groupe hospitalier Artois-Ternois. Hôpital Bichat and Université Paris Cité. CHU de Caen. Sorbonne Université. University Hospital, Brest. University Hospital, Clermont. Bordeaux University. University Hospital, Lenval. University Hospital, Dynamicure. University Hospital, Limoges. University Hospital, Montpellier. University Hospital, Toulouse. University Hospital, Rennes. Henri Mondor Hospital.
France
Pediatric Pulmonology
Pediatr Pulmonol 2025; 60:
DOI: 10.1002/ppul.71324
Abstract
Background: ATP-binding cassette transporter A3 (ABCA3) deficiency is one of the most severe causes of childhood interstitial lung diseases (chILD). This study aims to report the RespiRare ABCA3 cohort and to establish phenotype-genotype correlations.
Methods: Phenotypic and genotypic data of patients under 18 years were retrospectively included (1995-2023) in the RespiRare centers. The initial presentation and evolution of the subjects was analyzed depending on their genotype.
Results: The ABCA3 cohort comprised 36 children (30 families), including 5.5%, 22%, and 72% of null/null (no protein), null/other (potential residual function) and other/other genotypes respectively. A neonatal respiratory distress syndrome was observed in 31 (86%) subjects and 27 (75%) died at a median age of 3 months. The 5-year overall survival was 25% with an overall median survival of 0.33 year (IQR 0.09-4.43). A neonatal onset (p = 0.009) and the presence of pulmonary hypertension (p = 0.037) impaired the prognosis. At the last follow-up, the survival rates were 0/2 (0%), 4/8 (50%) and 6/26 (23%) in the null/null, null/other and other/other groups respectively. Eight of the 12 subjects who survived beyond 1 year carried at least one missense variant outside the nucleotide-binding domains (NBD) (n = 9) or the hypomorphic p.(Glu292Val) variant (n = 1).
Conclusion: The variable presentation and outcome of chILD due to ABCA3 pathogenic variants are linked to the underlying genotype. Neonatal onset, null variants, and variants involving the NBD are of peculiar severity.
Category
Class III. Pulmonary Hypertension Associated with Developmental Diseases of the Lung
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access Free
PDF File or Full Text Article Available Through PubMed or DOI: Yes