Ultrastructural characterization of genetic diffuse lung diseases in infants and children: a cohort study and review

Ultrastruct Pathol. 2013 Oct;37(5):356-65. doi: 10.3109/01913123.2013.811454.


Pediatric diffuse lung diseases are rare disorders with an onset in the neonatal period or in infancy, characterized by chronic respiratory symptoms and diffuse interstitial changes on imaging studies. Genetic disorders of surfactant homeostasis represent the main etiology. Surfactant protein B and ABCA3 deficiencies typically cause neonatal respiratory failure, which is often lethal within a few weeks or months. Although heterozygous ABCA3 mutation carriers are mostly asymptomatic, there is growing evidence that monoallelic mutations may affect surfactant homeostasis. Surfactant protein C mutations are dominant or sporadic disorders leading to a broad spectrum of manifestations from neonatal respiratory distress syndrome to adult pulmonary fibrosis. The authors performed pathology and ultrastructural studies in 12 infants who underwent clinical lung biopsy. One carried a heterozygous SP-B mutation, 3 carried SP-C mutations, and 7 carried ABCA3 mutations (5 biallelic and 2 monoallelic). Optical microscopy made it possible to distinguish between surfactant-related disorders and other forms. One of the ABCA3 monoallelic carriers had morphological features of alveolar capillary dysplasia, a genetic disorder of lung alveolar, and vascular development. One patient showed no surfactant-related anomalies but had pulmonary interstitial glycogenosis, a developmental disorder of unknown origin. Electron microscopy revealed specific lamellar bodies anomalies in all SP-B, SP-C, and ABCA3 deficiency cases. In addition, the authors showed that heterozygous ABCA3 mutation carriers have an intermediate ultrastructural phenotype between homozygous carriers and normal subjects. Lung biopsy is an essential diagnostic procedure in unexplained diffuse lung disorders, and electron microscopy should be performed systematically, since it may reveal specific alterations in genetic disorders of surfactant homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adolescent
  • Age Factors
  • Biopsy
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Glycogen Storage Disease / genetics
  • Glycogen Storage Disease / pathology
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Lung / metabolism
  • Lung / ultrastructure*
  • Lung Diseases / genetics
  • Lung Diseases / metabolism
  • Lung Diseases / pathology*
  • Lung Diseases, Interstitial / genetics
  • Lung Diseases, Interstitial / pathology
  • Male
  • Mutation
  • Persistent Fetal Circulation Syndrome / genetics
  • Phenotype
  • Pulmonary Alveolar Proteinosis / genetics
  • Pulmonary Alveolar Proteinosis / pathology
  • Pulmonary Alveoli / abnormalities
  • Pulmonary Alveoli / ultrastructure
  • Pulmonary Surfactant-Associated Proteins / deficiency
  • Pulmonary Surfactant-Associated Proteins / genetics
  • Rome


  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Pulmonary Surfactant-Associated Proteins

Supplementary concepts

  • Alveolar capillary dysplasia
  • Surfactant Dysfunction
  • Surfactant Metabolism Dysfunction, Pulmonary, 3