Journal of Inherited Metabolic Disease

, Volume 35, Issue 2, pp 253–261 | Cite as

Prediction of long-term outcome in glycine encephalopathy: a clinical survey

  • Julia B. Hennermann
  • Jeanne-Marie Berger
  • Ulrike Grieben
  • Gunter Scharer
  • Johan L. K. Van Hove
Original Article

Abstract

Objective

Glycine encephalopathy (GE) is a rare autosomal recessive inborn error of glycine degradation resulting in severe encephalopathy with ensuing poor outcome. Attenuated variants with a significantly better outcome have been reported. Early prediction of long-term outcome is not yet possible.

Methods

We compared the clinical and biochemical features of 45 children, each with a different course of the disease, to help determine predictors of long-term outcome.

Results

The most common presenting symptoms were hypotonia, seizures, and coma. In this study, 85% of the patients presented within the first week of life, and 15% presented after the neonatal period up to the age of 12 months. Developmental progress was made by 19% of those children presenting during the neonatal period and by 50% of those presenting in infancy. Initial CSF and plasma glycine concentrations were not useful in differentiating severe and attenuated outcome. A severe outcome was significantly associated with early onset of spasticity, frequent hiccupping, EEG burst-suppression or hypsarrhythmia patterns, microcephaly, and congenital or cerebral malformations, e.g. corpus callosum hypoplasia. An attenuated outcome was significantly associated with hyperactivity and choreiform movement disorders. We describe a severity score which facilitates the prediction of the outcome in patients with GE.

Conclusion

Prediction of the outcome of GE may be facilitated by recognizing selected clinical parameters and early neuroimaging findings.

Abbreviations

GCS

Glycine cleavage system

GE

Glycine encephalopathy

NMDA

N-methyl-D-aspartate

Notes

Acknowledgement

We thank all the children and their parents for participation and for their cooperation.

Special thanks to the cooperating colleagues G. Froese, Böblingen, Germany; S. Stolz, Cottbus, Germany; U. Spiekerkötter and U. Wendel, Düsseldorf, Germany; I. Knerr, Erlangen, Germany; J. Herwig, Frankfurt, Germany; W. Lehnert, Freiburg, Germany; J. Kreuder, Giessen, Germany; G. F. Hoffmann, Heidelberg, Germany; T. Marquardt, Münster, Germany; R. Ensenauer, Munich, Germany; F. K. Trefz and H. Korall, Reutlingen, Germany; F. Walter, Rostock, Germany; M. Häussler, Würzburg, Germany; C. Nuttin, Luxembourg; J Smeitink and R Sengers, Nijmegen, The Netherlands; J. Jaeken, Leuven, Belgium; and the general practitioners.

We thank Dr. Janet Thomas, MD for her careful review of the manuscript and constructive comments.

We thank Nutricia/SHS, Heilbronn, Germany, for support of J-M Berger. JLK Van Hove and G Scharer are supported by the NKH Crusader Fund and the Hope for NKH Fund.

Disclosure

Travelling expenses for J-M Berger were overtaken by Nutricia/SHS, Heilbronn, Germany.

Supplementary material

10545_2011_9398_MOESM1_ESM.doc (24 kb)
ESM 1 (DOC 23.5 kb)

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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Julia B. Hennermann
    • 1
  • Jeanne-Marie Berger
    • 1
    • 2
  • Ulrike Grieben
    • 3
    • 4
  • Gunter Scharer
    • 5
  • Johan L. K. Van Hove
    • 5
    • 6
  1. 1.Department of PediatricsCharité UniversitätsmedizinBerlinGermany
  2. 2.Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyMedizinische Einrichtungen des Bezirks OberpfalzRegensburgGermany
  3. 3.Department of NeuropediatricsCharité UniversitätsmedizinBerlinGermany
  4. 4.Experimental and Clinical Research Center, A Joint Cooperation Between Charité Medical Faculty and the Max-Delbrück Center for Molecular MedicineBerlinGermany
  5. 5.Department of PediatricsUniversity of ColoradoAuroraUSA
  6. 6.Department of PediatricsKatholieke Universiteit LeuvenLeuvenBelgium

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