Skip to main content

Thank you for visiting 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.

Neonatal lactic acidosis explained by LARS2 defect

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Zecic, A. et al. Lactic acidosis in a newborn with adrenal calcifications. Pediatr. Res. 66, 317–322 (2009).

    CAS  Article  Google Scholar 

  2. Meyer-Schuman, R. & Antonellis, A. Emerging mechanisms of aminoacyl-tRNA synthetase mutations in recessive and dominant human disease. Hum. Mol. Genet. 26, R114–R127 (2017).

    CAS  Article  Google Scholar 

  3. Pierce, S. B. et al. Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome. Am. J. Hum. Genet. 92, 614–620 (2013).

    CAS  Article  Google Scholar 

  4. Riley, L. G. et al. LARS2 variants associated with hydrops, lactic acidosis, sideroblastic anemia, and multisystem failure. JIMD Rep. 28, 19–57 (2016).

    Google Scholar 

  5. Solda, G. et al. First independent replication of the involvement of LARS2 in Perrault syndrome by whole-exome sequencing of an Italian family. J. Hum. Genet. 61, 295–300 (2016).

    CAS  Article  Google Scholar 

  6. Lerat, J. et al. An application of NGS for molecular investigations in Perrault syndrome: study of 14 families and review of the literature. Hum. Genet. 37, 1354–1362 (2016).

    CAS  Google Scholar 

  7. Demain, L. A. M. et al. Expanding the genotype spectrum of Perrault syndrome. Clin. Genet. 91, 302–312 (2017).

    CAS  Article  Google Scholar 

  8. Kosaki, R., Horikawa, R., Fujii, E. & Kosaki, K. Biallelic mutations in LARS2 can cause Perrault syndrome type 2 with neurologic symptoms. Am. J. Med. Genet. 176, 404–408 (2018).

    CAS  Article  Google Scholar 

  9. van der Knaap, M. S. et al. Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy. Neurology 92, 1225–1236 (2019).

    Article  Google Scholar 

  10. Carminho-Rodrigues, M. T. et al. LARS2-Perrault syndrome: a new case report and literature review. BMC Med. Genet. 21, e109 (2020).

    Article  Google Scholar 

  11. Riley, L. G. et al. The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy. Hum. Mutat. 41, 1425–1434 (2020).

    CAS  Article  Google Scholar 

  12. Pan, Z. et al. Perrault syndrome: clinical report and retrospective analysis. Mol. Genet. Genom. Med. 8, e1445 (2020).

    CAS  Google Scholar 

  13. Buonfiglio, P. I. et al. Predicting pathogenicity for novel hearing loss mutations based on genetic and protein structure approaches. Sci. Rep. 12, e301 (2022).

    Article  Google Scholar 

  14. Schwarz, J. M., Cooper, D. N., Schuelke, M. & Seelow, D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat. Methods 11, 361–362 (2014).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations



Conceptualization and data curation: B.D.P., J.S., R.K. and A.V.; formal analysis and methodology: A.V., R.V.C. and H.P.; project administration, resources and supervision: R.V.C. and A.V.; manuscript draft preparation: B.D.P.; review, editing and approval of the final version: all authors.

Corresponding author

Correspondence to Boel De Paepe.

Ethics declarations

Competing interests

R.V.C. and A.V. are members of the European Reference Network for Hereditary Metabolic Disorders, MetabERN. The remaining authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

De Paepe, B., Smet, J., Kopajtich, R. et al. Neonatal lactic acidosis explained by LARS2 defect. Pediatr Res (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


Quick links