Prediction of long-term outcome in glycine encephalopathy: a clinical survey
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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.
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.
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.
Prediction of the outcome of GE may be facilitated by recognizing selected clinical parameters and early neuroimaging findings.
KeywordsVigabatrin Club Foot Dextromethorphan Felbamate Glycine Cleavage System
Glycine cleavage system
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.
Travelling expenses for J-M Berger were overtaken by Nutricia/SHS, Heilbronn, Germany.
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