Original article Nonketotic hyperglycinemia: Clinical range and outcome of a rare neurometabolic disease in a single-center C ¸ ig ˘dem Genc ¸ Sel a,⇑ , Mustafa Kılıc ¸ b , Deniz Yu ¨ksel a , Ays ße Aksoy a , C ¸ ig ˘dem Seher Kasapkara b , Serdar Ceylaner c , Kader Karlı Og ˘uz d a Dr. Sami Ulus Pediatric and Training Hospital, Pediatric Neurology Department, Ankara, Turkey b Dr. Sami Ulus Pediatric and Training Hospital, Pediatric Metabolism Department, Ankara, Turkey c Laborotory of Genetics Intergene, Genetics Department, Ankara, Turkey d Hacettepe University of Faculty of Medicine, Radiology Department, Neuroradiology Division, Ankara, Turkey Received 9 September 2017; received in revised form 26 May 2018; accepted 8 June 2018 Abstract Background: Nonketotic hyperglycinemia (NKH) is an autosomal recessive severe life-threatening catostrophic metabolic disorder. Materials and methods: The present study was conducted in a tertiary reference center in Turkey for six years period. The accu- rate diagnosis of six NKH patients was based on clinical history of the patients, neurological examinations, seizure semiology, serial electroencephalography (EEG) recordings, neuroimaging findings, metabolic tests and genetic analysis. Results: The common clinical findings were hypotonia with severe head lag, poor feeding, poor sucking, and intractable seizures. The starting age of the symptoms was between birth and 45 days of age (median: 8 days). The starting age of the seizures was between 30 min of age and 45 days of age (median: 18 days). The age of accurate diagnosis was between 1 month of age and 5.5 months of age (mean: 3.75 ± 1.69 months). The cerebrospinal fluid (CSF) to plasma GLY ratio of the patients was between 0.031 and 0.21 (median: 0.16). The EEG patterns of the patients were suppression-burst, hypsarrhythmia, multifocal epileptic activ- ity, and right centro-occipital epileptic activity on admission. The neuroimaging findings were diffuse hypomyelination, corpus cal- losum (CC) hypoplasia, CC agenesis and brainstem hypoplasia on the magnetic resonance imaging and glycine peak was evidenced on magnetic resonance spectroscopy. Four of the patients were mutation-positive. Conclusions: If a child is encephalopathic and/or hypotonic with severe head lag, early evaluation of the EEG records should be made even without a history of clinical seizures. The disease has a heterogenous course and the clinical outcome depends on the mutation type. Ó 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Nonketotic hyperglycinemia; Glycine encephalopathy; Intractable seizures; Hiccups; Severe hypotonia; Mutation type; Outcome 1. Introduction Glycine (GLY) encephalopathy or nonketotic hyper- glycinemia (NKH) is caused by a biochemical defect in the GLY cleavage system [1]. This system is an enzy- matic system located in the inner mitochondrial mem- branes of the brain, liver, kidney, placental cells, and https://doi.org/10.1016/j.braindev.2018.06.007 0387-7604/Ó 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. ⇑ Corresponding author at: Doctor Sami Ulus Pediatric and Train- ing Hospital, Department of Pediatric Neurology, Babu ¨r Street, No: 44, 06080, Altındag ˘, Ankara, Turkey. E-mail address: cigdemsel@yahoo.com (C ¸ . Genc ¸ Sel). www.elsevier.com/locate/braindev Brain & Development xxx (2018) xxx–xxx Please cite this article in press as: Genc ¸ Sel C ¸ et al. Nonketotic hyperglycinemia: Clinical range and outcome of a rare neurometabolic disease in a single-center. Brain Dev (2018), https://doi.org/10.1016/j.braindev.2018.06.007