A83-04 ABCA3-related Surfactant Dysfunction Mimicking Eosinophilic Pneumonia in a Preschool Child

Introduction

Diffuse lung disease in preschool children is a heterogenous group of disorders that encompasses diverse etiologies, with established algorithms for diagnosis and treatment. Rarely, cases may defy established diagnostic frameworks, necessitating more nuanced and integrative approaches. We present the case of a child with recurrent respiratory infections, respiratory distress and hypoxia, prompting detailed evaluation and multidisciplinary evaluation for definitive diagnosis.

Case

A previously healthy 4-year-old boy presented to our center for evaluation of progressive diffuse lung disease. His symptoms started 4 months prior with recurrent episodes of viral pneumonia/ bronchiolitis, progressing to respiratory distress and hypoxia. Evaluation at an outside institution included computed tomography (CT) (Figure 1) showing peripheral ground-glass opacities consistent with a reverse pulmonary edema pattern; bronchoalveolar lavage (BAL) with 40% eosinophils and high adenovirus titers; and a right lower lobe transbronchial biopsy demonstrating organizing pneumonia. He was treated with high dose pulse methylprednisolone and inhaled corticosteroids (ICS) for presumed eosinophilic pneumonia and considered for biologic therapy. Despite transient improvement, he had recurrent respiratory distress and increased oxygen requirements, requiring frequent pulse steroids. At initial presentation, examination revealed BMI<3rd percentile, right upper lobe crackles and digital clubbing. Review of records revealed prior genetic testing with two ABCA3 variants of uncertain significance (VUS); parental testing and whole exome sequencing (WES) was sent. Further evaluation for eosinophilic lung disease was negative and detailed cytokine analysis showed elevated IL-6, IL-10, and TNF levels. Repeat BAL demonstrated persistent eosinophilia with absence of peripheral blood eosinophilia. A video-assisted thoracoscopic (VATS) right upper lobe biopsy revealed chronic interstitial inflammation, patchy pulmonary alveolar proteinosis, and abnormal lamellar bodies on electron microscopy (Figure 2). Parental testing confirmed ABCA3 variants in trans, establishing a diagnosis of surfactant dysfunction disorder secondary to ABCA3 mutations; no additional mutations were identified on WES. We initiated therapy with hydroxychloroquine and azithromycin, continued ICS and tapered systemic corticosteroids. The patient showed marked improvement, with resolution of cough, improved activity tolerance, and weight gain. Ongoing management focuses on long-term optimization, monitoring steroid dependence, evaluating biologic therapy, and clarifying variant pathogenicity.

Discussion

This case highlights how surfactant dysfunction disorders can masquerade as another diffuse lung disease. In diagnostically challenging cases, an adequate lung biopsy from affected regions can serve as the gold standard. Additionally, ABCA3 variants may present later with milder phenotypes highlighting the wide spectrum of ABCA3-related surfactant dysfunction.

This abstract is funded by: None