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

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.