Published online Aug 6, 2022. doi: 10.12998/wjcc.v10.i22.7982
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
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.
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 treat
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.
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.