Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perinatal/Neonatal Case Presentation
  • Published:

Perinatal/Neonatal Case Presentation

Unimpaired postnatal respiratory adaptation in a preterm human infant with a homozygous ENaC-α unit loss-of-function mutation

Journal of Perinatology volume 31, pages 802–803 (2011)Cite this article

Subjects

Abstract

The amiloride-sensitive epithelial sodium channel, ENaC, is thought to have a major role in clearing fluid from the alveoli immediately after birth. ENaC-α knockout mice die soon after birth from failure to clear their lungs of liquid. We report on a male infant born after 33 weeks of gestation with uneventful postnatal adaptation (Apgar 9/9/9 at 1, 5 and 10 min after birth) who did not require any respiratory support during his first days of life. At nine days of life, he became lethargic and hyperthermic, displaying low Na+ (126 mmol l−1), high K+ (8.9 mmol l−1), high aldosterone (3000 ng l−1)and high renin (1000 ng l−1) plasma concentrations, commensurate with pseudohypoaldosteronism type I. He was found to be homozygous for the c.1678G>A mutation in the SCNN1A gene that codes for the ENaC-α unit. We conclude that clearance of alveolar fluid after birth in humans does not critically depend on ENaC.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hallman M . Delayed clearance of fetal lung liquid and sodium transport—genetic predisposition not evident yet. Acta Pædiatr 2005; 94: 258–260.

    PubMed  Google Scholar 

  2. Helve O, Pitkänen O, Janér C, Andersson S . Pulmonary fluid balance in the human newborn infant. Neonatology 2009; 95: 347–352.

    Article  Google Scholar 

  3. O’Brodovich H, Hannam V, Seear M, Mullen JB . Amiloride impairs lung water clearance in newborn guinea pigs. J Appl Physiol 1990; 68: 1758–1762.

    Article  Google Scholar 

  4. Hummler E, Barker P, Gatzy J, Beermann F, Verdumo C, Schmidt A et al. Early death due to defective neonatal lung liquid clearance in α-ENaC-deficient mice. Nat Genet 1996; 12: 325–328.

    Article  CAS  Google Scholar 

  5. Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, Hanukoglu I et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type I. Nat Genet 1996; 12: 248–253.

    Article  CAS  Google Scholar 

  6. Kerem E, Bistritzer T, Hanukoglu A, Hofmann T, Zhou Z, Bennett W et al. Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism. N Engl J Med 1999; 341: 156–162.

    Article  CAS  Google Scholar 

  7. Hanukoglu A, Bistritzer T, Rakover Y, Mandelberg A . Pseudohypoaldosteronism with increased sweat and saliva electrolyte values and frequent lower respiratory tract infections mimicking cystic fibrosis. J Pediatr 1994; 125: 752–755.

    Article  CAS  Google Scholar 

  8. Schaedel C, Marthinsen L, Kristoffersson AC, Kornfalt R, Nilsson KO, Orlenius B et al. Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the α-subunit of the epithelial sodium channel. J Pediatr 1999; 135: 739–745.

    Article  CAS  Google Scholar 

  9. Akçay A, Yavuz T, Semiz S, Bundak R, Demirdöven M . Pseudohypoaldosteronism type 1 and respiratory distress syndrome. J Pediatr Endocrinol Metab 2002; 15: 1557–1561.

    Article  Google Scholar 

  10. Eaton DC, Helms MN, Koval M, Bao HF, Jain L . The contribution of epithelial sodium channels to alveolar function in health and disease. Annu Rev Physiol 2009; 71: 403–423.

    Article  CAS  Google Scholar 

  11. O’Brodovich H, Yang P, Gandhi S, Otulakowski G . Amiloride-insensitive Na+ and fluid absorption in the mammalian distal lung. Am J Physiol Lung Cell Mol Physiol 2008; 294: L401–L408.

    Article  Google Scholar 

  12. Bonny O, Chraibi A, Loffing J, Jaeger NF, Gründer S, Horisberger JD et al. Functional expression of a pseudohypoaldosteronism type I mutated epithelial Na+ channel lacking the pore-forming region of its alpha subunit. J Clin Invest 1999; 104: 967–974.

    Article  CAS  Google Scholar 

  13. Husted RF, Volk KA, Sigmund RD, Stokes JB . Discordant effects of corticosteroids and expression of subunits on ENaC activity. Am J Physiol Renal Physiol 2007; 293: F813–F820.

    Article  CAS  Google Scholar 

  14. Nakamura K, Stokes JB, McCray Jr PB . Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung. Am J Physiol Cell Physiol 2002; 283: C762–C772.

    Article  CAS  Google Scholar 

  15. McDonald FJ, Yang B, Hrstka RF, Drummond HA, Tarr DE, McCray Jr PB et al. Disruption of the beta subunit of the epithelial Na+ channel in mice: hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype. Proc Natl Acad Sci USA 1999; 96: 1727–1731.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Maria Christina Zennaro, DR2 INSERM U772, Collège de France, 11 place Marcelin Berthelot, F-75005 Paris, France for molecular analysis of the SCNN1A gene.

Author information

Authors and Affiliations

  1. Department of Neonatology, Charité University Medical Center, Berlin, Germany

    S Huppmann & C Bührer

  2. Department of Pediatric Endocrinology, Charité University Medical Center, Berlin, Germany

    E Lankes & D Schnabel

Authors
  1. S Huppmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Lankes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Schnabel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Bührer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Bührer.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huppmann, S., Lankes, E., Schnabel, D. et al. Unimpaired postnatal respiratory adaptation in a preterm human infant with a homozygous ENaC-α unit loss-of-function mutation. J Perinatol 31, 802–803 (2011). https://doi.org/10.1038/jp.2011.46

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2011.46

Keywords

Search

Advanced search

Quick links