C95-03 Abca 3 Related Pulmonary Disease in Colombia: Genotype Matters in the Hidden Burden of Intronic Mutations

Rationale the ABCA3 transporter plays an essential role in pulmonary surfactant regulation. Pathogenic variants in ABCA3 represent the most significant monogenic cause of lethal neonatal respiratory failure and pediatric interstitial lung disease. This autosomal recessive disorder has an estimated incidence of 1 in 3,000–18,000 live births and displays wide clinical heterogeneity. In Colombia, anecdotal reports have described intronic variants associated with severe early-onset disease, but no formal registry exists. This study aimed to describe the genotypic and phenotypic characteristics of children with ABCA3 mutations managed in two Colombian cities over the past ten years. Methods we conducted an observational, descriptive, retrospective study of patients with confirmed ABCA3 mutations between 2015 and 2025. Qualitative and quantitative variables were extracted from medical records and were analyzed using SPSS version 30. Results fifteen patients were included, 66.7% male. The median age at first evaluation was 1 month (IQR=0–4), with symptom onset during the neonatal period in 12 patients. Median gestational age was 39 + 0 weeks (IQR=37 + 5–40 + 0), all with adequate birth weight. No consanguinity was reported, but 33.3% had a family history of early lethal lung disease. Respiratory failure was the most striking initial finding for the medical team (53.3%), with desaturation in 93.3%, tachypnea in 86.7%, and failure to thrive in 46.7%. Pulmonary hypertension occurred in 10 patients(66.7%). All chest CTs showed diffuse ground-glass opacities. Six (60%) underwent lung biopsy, all demonstrating type II pneumocyte hyperplasia and alveolar septal thickening. The intronic variant c.3863-98C>T was detected in 10 patients(66.7%) in homozygosity and in 5 patients as compound heterozygotes, three carrying this variant on one allele. Respiratory infections were documented in 53.3% of patients, most frequently due to rhinovirus (50% of the episodes). Systemic corticosteroids were used in 80%, azithromycin in 53.3%, and hydroxychloroquine in 46.7%; five required home oxygen therapy. Overall mortality reached 66.7%, with a median age at death of 1 month (IQR=0–5); 90% of deceased patients were homozygous. Conclusions we describe the largest Colombian series of ABCA3-related pulmonary disease, characterized by severe neonatal onset and high mortality among homozygous carriers of the intronic variant. Our findings reinforce this mutation as a likely founder variant in the Colombian population. A previously reported carrier frequency of 1.9% and an estimated incidence of one affected newborn per 11,000 births underscore its epidemiologic relevance. These results highlight the importance of implementing region-specific molecular studies capable of detecting deep intronic variants often missed. This abstract is funded by: None