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.

  • Case Report
  • Published:

Ketogenic diet, a potentially valuable therapeutic option for the management of refractory epilepsy in classical neonatal nonketotic hyperglycinemia: a case report

European Journal of Clinical Nutrition volume 73, pages 961–965 (2019)Cite this article

Subjects

Abstract

Nonketotic hyperglycinemia (NKH) is a devastating inborn error of glycine metabolism caused by deficient activity of the glycine cleavage enzyme. Classically, patients present with lethargy, hypotonia, myoclonic jerks, transient respiratory depression in the first week of life and often progress to death. Surviving infants have profound psychomotor retardation, refractory epilepsy and poor quality of life. Currently, no effective therapeutic avenues exist for severe NKH. Ketogenic diet (KD) has been trialled only in a small group of patients with neonatal NKH and early myoclonic encephalopathy, in whom significant improvements in seizure control were reported. We describe an infant with classical neonatal NKH who presented on the third day of life with hypotonia, poor feeding, respiratory insufficiency resulting in ventilatory support and seizures with burst-suppression pattern on electroencephalogram (EEG). KD initiated at age 6 months for intractable seizures, lead to a dramatic decrease in seizure frequency, EEG improvements, normalisation of plasma glycine levels, reduced spasticity and improved quality of life. KD may be a valuable treatment modality for refractory seizure control in classical NKH.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Van Hove J, Coughlin C II, Scharer G. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2017. Updated 11 July 2013.

  2. Ohya Y, Ochi N, Mizutani N, Hayakawa C, Watanabe K. Nonketotic hyperglycinemia: Treatment with NMDA antagonist and consideration of neuropathogenesis. Pediatr Neurol. 1991;7:65–68.

    Article  CAS  Google Scholar 

  3. Hennermann JB, Berger JM, Grieben U, Scharer G, Van Hove JL. Prediction of long-term outcome in glycine encephalopathy: a clinical survey. J Inherit Metab Dis. 2012;35:253–61.

    Article  CAS  Google Scholar 

  4. Swanson MA, Coughlin CR, Scharer GH, Szerlong HJ, Bjoraker KJ, Spector EB, et al. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia. Ann Neurol. 2015;78:606–18.

    Article  CAS  Google Scholar 

  5. Jaeken J, de Koning T, van Hove J. Disorders of GABA, glycine, serine and proline. In: Blau N, Duran M, Blaskovics ME, Gibson KM, editors. Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases. 2nd ed. Berlin: Springer; 2002. p. 123–40.

    Google Scholar 

  6. Cusmai R, Martinelli D, Moavero R, Dionisi Vici C, Vigevano F, Castana C, et al. Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia. Eur J Pediatr Neurol. 2012;16:509–13.

    Article  Google Scholar 

  7. Bzduch V, Behulova D, Kolnikova M, Payerova J, Fabriciova K. Ketogenic diet in nonketotic hyperglycinemia. J Inherit Metab Dis. 2010;33(S1):S31.

    Google Scholar 

  8. Nickerson SL, Balasubramaniam S, Dryland PA, Love JM, Kava MP, Love DR, et al. Two novel GLDC mutations in a neonate with nonketotic hyperglycinemia. J Pediatr Genet. 2016;5:174–80.

    Article  CAS  Google Scholar 

  9. Nylen K, Likhodii S, Burnham WM. The ketogenic diet: proposed mechanisms of action. Neurotherapeutics. 2009;6:402–5.

    Article  CAS  Google Scholar 

  10. Bough K. Energy metabolism as part of the anti-convulsant mechanism of the ketogenic diet. Epilepsia. 2009;49:91–93.

    Article  Google Scholar 

  11. Busanello ENB, Moura AP, Viegas CM, Zanatta A, da Costa Ferreira G, Schuck PF, et al. Neurochemical evidence that glycine induces bioenergetical dysfunction. Neurochem Int. 2010;56:948–54.

    Article  CAS  Google Scholar 

  12. Seminotti B, Knebel LA, Fernandes GC, Amaral AU, da Rosa MS, Eichler P, et al. Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defences in rat brain. Life Sci. 2011;89:276–81.

    Article  CAS  Google Scholar 

  13. Samoilova M, Weisspapir M, Abdelmalik P, Velumian AA, Carlen PL. Chronic in vitro ketosis is neuroprotective but not anti-convulsant. J Neurochem. 2010;113:826–35.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Princess Margaret Hospital for Children, Perth, WA, Australia

    Maina P. Kava

  2. School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia

    Maina P. Kava & Shanti Balasubramaniam

  3. Metabolic Unit, Department of Rheumatology and Metabolic Medicine, Princess Margaret Hospital, Perth, WA, Australia

    Maina P. Kava & Shanti Balasubramaniam

  4. Dietetics Department, Princess Margaret Hospital, Perth, WA, Australia

    Annie Robertson

  5. PathWest Laboratory Medicine WA, Princess Margaret Hospital, Perth, WA, Australia

    Lawrence Greed

  6. Western Sydney Genetics Program, Children’s Hospital at Westmead, Sydney, NSW, Australia

    Shanti Balasubramaniam

  7. Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

    Shanti Balasubramaniam

Authors
  1. Maina P. Kava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annie Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence Greed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shanti Balasubramaniam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maina P. Kava.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kava, M.P., Robertson, A., Greed, L. et al. Ketogenic diet, a potentially valuable therapeutic option for the management of refractory epilepsy in classical neonatal nonketotic hyperglycinemia: a case report. Eur J Clin Nutr 73, 961–965 (2019). https://doi.org/10.1038/s41430-018-0286-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-018-0286-8

This article is cited by

Search

Advanced search

Quick links