Interstitial lung disease in children: ultra-rare genetic variants from national registry of Türkiye

Abstract

The advancement of genetic analysis techniques has led to identifying novel genetic entities in children’s interstitial lung disease(chILD). We aimed to showcase diverse demographic, clinical, radiological, and laboratory data regarding these ultra-rare genetic variants in chILD via a national registry. Method: We analyzed data from the chILD-Türkiye registry, focusing on ultra-rare genetic chILD subtypes. Of the 671 patients,182 underwent genetic analysis,44 with ultra-rare genetic variants included in the study with their demographic and clinical data. Results: Of the patients,23(52.3%) were female. The median gestational age was 38.5 weeks(IQR 37.2-40);5(11.4%) had been on a mechanical ventilator in the neonatal intensive care unit,30(68.2%) had familial consanguinity,25(56.8%) had systemic disease. All patients had chest CT scans during their initial assessment, showing ground-glass opacities in 34 patients(77.3%), infiltrations in 31(70.5%), and interlobular septal thickening in 23(52.3%). The genetic analysis conducted on 11 patients had variations in the COPA, STAT3, STING1, ADA, ZNFX1, PIK3CD, PLCG2, and ATM genes, which are linked to immunodeficiency/immune dysregulation;11 had variations in NPC1, A1, SLC7A7 genes which are linked to inborn errors of metabolism. Variations were found in genes CCR2, TBX4, OAS1, TERT, MARS1, FARSB, SLC34A2, RTEL1, PLG, MUC5B, RNF168, PEPD, and SMAD4 in 22 patients. Thirteen patients (29.5%) received oral, and 9(20.4%) pulse steroids in addition to their primary treatments for systemic diseases. Conclusions: ChILD is rare in children, but increased genetic analysis can enable earlier diagnosis. Recognizing chILD may occur in rare systemic diseases can improve outcomes.