Background: Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborns and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations focused primarily on the genetic abnormalities and reported limited clinical information about the resultant disease.
Objective: To systematically analyze the clinical presentation, pulmonary function, diagnostic imaging, pathologic features, and outcomes of children with ABCA3 mutations.
Methods: The records of nine children with ABCA3 mutations evaluated at Texas Children's Hospital between 1992 and 2005 were reviewed and their current clinical status updated. Previous diagnostic imaging studies and lung biopsy specimens were reexamined. Results of DNA analyses were confirmed.
Results: Age at symptom onset ranged from birth to four years. Cough, crackles, failure to thrive, and clubbing were frequent findings. Mean lung function was low but tended to remain static. Computed tomography scans commonly revealed ground-glass opacification, septal thickening, parenchymal cysts, and pectus excavatum. Histopathologic patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis, and nonspecific interstitial pneumonitis and varied with age. Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens. Outcomes varied with the age at which the severity of lung disease warranted open lung biopsy, and some patients have had prolonged survival without lung transplantation.
Conclusions: The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.
- interstitial lung disease
- surfactant deficiency