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.