Case Report
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 6, 2022; 10(22): 7982-7988
Published online Aug 6, 2022. doi: 10.12998/wjcc.v10.i22.7982
Clinical and genetic analysis of nonketotic hyperglycinemia: A case report
Jun-Jie Ning, Feng Li, Sheng-Qiu Li
Jun-Jie Ning, Feng Li, Sheng-Qiu Li, Department of Pediatric Intensive Care Unit, First People's Hospital of Zigong City, Zigong 643000, Sichuan Province, China
Author contributions: Ning JJ and Li F were the patient’s doctors; Ning JJ reviewed the literature, contributed to drafting the manuscript, and provided plans for the treatment; Li SQ was the nurse in charge of the child.
Informed consent statement: The patient’s parents provided informed written consent for the publication of this case report.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun-Jie Ning, MD, Attending Doctor, Department of Pediatric Intensive Care Unit, First People's Hospital of Zigong City, No. 42 Shangyi Haozhi Road, Zigong 643000, Sichuan Province, China. 196425984@qq.com
Received: January 12, 2022
Peer-review started: January 12, 2022
First decision: May 11, 2022
Revised: May 19, 2022
Accepted: July 5, 2022
Article in press: July 5, 2022
Published online: August 6, 2022
Processing time: 191 Days and 2.5 Hours
Abstract
BACKGROUND

Nonketotic hyperglycinemia (NKH) is a rare autosomal recessive genetic disorder of abnormal glycine metabolism caused by insufficient activity of the glycine cleavage enzyme system. Glycine is believed to function mainly as an inhibitory neurotransmitter, but it can also act as a co-agonist of the N-methyl-D-aspartate (NMDA) receptor. The accumulation of a large amount of glycine in the brain leads to neuronal and axonal injury via overactivation of NMDA receptors located in the hippocampus, cerebral cortex, olfactory bulb, and cerebellum and to stimulation of the inhibitory function of glycine receptors located in the spinal cord and brain stem, resulting in central apnea, hiccups, and hypotonia in the early stage of the disease.

CASE SUMMARY

The child described in this report had typical clinical manifestations of NKH, such as hiccups, disturbance of consciousness, hypotonia, and convulsions, within the first week after birth. Whole-exome genetic testing revealed that the child had a compound heterozygous mutation, namely, c.395C>A (p.S132X) and c.2182G>A (p.G728R), in the GLDC gene, and he was diagnosed with NKH. For treatment, we administered an oral levetiracetam solution and added topiramate and prednisone for epilepsy control, but the epilepsy remained uncontrollable. Ketogenic diet therapy was started at 6 mo of age, his seizures were significantly reduced, and there were no obvious adverse reactions during ketogenic treatment. Furthermore, we found that with the development of the disease, high levels of serum glycine decreased or even disappeared without intervention, and as the disease progressed, the corpus callosum became dysplastic.

CONCLUSION

This case shows that plasma glycine levels cannot be used to evaluate the prognosis of NKH, that the development of the corpus callosum can be affected by NKH, and that a ketogenic diet may be effective for seizure control in NKH patients.

Keywords: Nonketotic hyperglycinemia; Compound heterozygosity; GLDC gene; Case report

Core Tip: Herein, we present the case of a child who had typical clinical manifestations of nonketotic hyperglycinemia (NKH), such as hiccups, disturbance of consciousness, hypotonia, and convulsions within the first week after birth. These symptoms combined with the results of gene testing led to a diagnosis of classical nonketotic hyperglycinemia caused by compound heterozygous variants in the GLDC gene. Plasma glycine levels cannot be used to evaluate the prognosis of NKH, and the corpus callosum can be affected by NKH. A ketogenic diet may be effective for seizure control in NKH patients.