A Hereditary Pulmonary Alveolar Proteinosis Caused by a Novel Hemizygous Variation of the CSF2RA Gene Case Report and Literature Review

Background Hereditary pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease caused by variations in genes such as CSF2RA and CSF2RB , which disrupt granulocyte‐macrophage colony‐stimulating factor signaling and impair surfactant clearance. These defects lead to progressive surfactant accumulation in alveoli, resulting in respiratory dysfunction. Methods We describe a 3‐year‐old girl with Turner syndrome who presented with recurrent cough and dyspnea and was diagnosed with hereditary PAP. Diagnostic evaluation included high‐resolution computed tomography (HRCT), lung biopsy, and whole‐exome sequencing of peripheral blood cells. The patient received anti‐inflammatory antibiotics and underwent therapeutic whole lung lavage via endobronchial endoscopy. A systematic literature review of CSF2RA ‐associated hereditary PAP was performed. Results HRCT demonstrated characteristic “crazy paving” patterns, and bronchoalveolar lavage fluid showed positive Periodic acid‐Schiff staining. Genetic analysis identified a novel hemizygous variation in CSF2RA (NM_000402.4:c.200_204del, p.Asn67SerfsTer8), confirmed as a de novo pathogenic variant. Whole lung lavage resulted in marked clinical improvement. Conclusions We report the first documented case of hereditary PAP caused by the CSF2RA variant NM_000402.4:c.200_204del (p.Asn67SerfsTer8), expanding the genetic spectrum of this disease. Our findings reinforce that CSF2RA ‐related PAP exhibits phenotypic heterogeneity and confirm whole lung lavage as the cornerstone therapy. This case highlights the importance of genetic testing in diagnosing rare PAP subtypes.