An Exceptional Cause of Diffuse Interstitial Pneumonia in Children: Genetic Pulmonary Alveolar Proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by intra-alveolar accumulation of lipoproteinaceous material due to defective surfactant clearance by alveolar macrophages. In children, genetic forms mainly involve mutations of surfactant-related genes (SFTPB, SFTPC, ABCA3) and the GM-CSF receptor. We report the case of a 13-year-old girl born to consanguineous parents, presenting since age 3 with chronic dry cough and progressive exertional dyspnea. Chest CT revealed diffuse ground-glass opacities with a crazy-paving pattern. Bronchoalveolar lavage (BAL) yielded a milky fluid containing PAS-positive lipoproteinaceous material. Genetic analysis identified a mutation in the α-chain of the GM-CSF receptor. The patient underwent repeated whole-lung lavage procedures with gradual clinical and radiological improvement. Therapeutic lung lavage remains the standard of care, though newer approaches, such as inhaled or subcutaneous GM-CSF, plasma exchange, and rituximab, aim to restore macrophage function. Recent series report markedly improved survival, approaching 95 %.