Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis
Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and cong...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442541/ https://www.ncbi.nlm.nih.gov/pubmed/37614902 http://dx.doi.org/10.3389/fped.2023.1155035 |
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author | Thewamit, Rapeepat Khongkhatithum, Chaiyos Thampratankul, Lunliya Kamolvisit, Wuttichart Khongkrapan, Arthaporn Wattanasirichaigoon, Duangrurdee |
author_facet | Thewamit, Rapeepat Khongkhatithum, Chaiyos Thampratankul, Lunliya Kamolvisit, Wuttichart Khongkrapan, Arthaporn Wattanasirichaigoon, Duangrurdee |
author_sort | Thewamit, Rapeepat |
collection | PubMed |
description | Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the GLDC gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1–2 deletion in the GLDC gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate–related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the PROC gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause. |
format | Online Article Text |
id | pubmed-10442541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104425412023-08-23 Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis Thewamit, Rapeepat Khongkhatithum, Chaiyos Thampratankul, Lunliya Kamolvisit, Wuttichart Khongkrapan, Arthaporn Wattanasirichaigoon, Duangrurdee Front Pediatr Pediatrics Nonketotic hyperglycinemia (NKH) is in most cases a fatal inborn error of metabolism which usually presents during the neonatal period as encephalopathy and refractory seizures. The reported congenital anomalies associated with NKH included corpus callosal agenesis, club foot, cleft palate, and congenital heart disease. Here, we report a newborn who presented with encephalopathy without overt seizures, cerebral venous sinus thrombosis, and cleft palate. Electroencephalography showed a burst suppression pattern, which suggests the etiology could be due to a metabolic or genetic disorder. The amino acid analysis of plasma and cerebrospinal fluid showed elevated glycine. Whole exome sequencing identified a heterozygous c.492C > G; p.Tyr164Ter variant in exon 4 of the GLDC gene inherited from the patient's father. Further long-read whole genome sequencing revealed an exon 1–2 deletion in the GLDC gene inherited from the patient's mother. Additional analyses revealed no pathogenic variants of the cleft palate–related genes. The cleft palate may be an associated congenital anomaly in NKH. Regarding cerebral venous sinus thrombosis, we found a heterozygous variant (p.Arg189Trp) of the PROC gene, which is a common cause of thrombophilia among Thai newborns. A neonate with NKH could present with severe encephalopathy without seizures. A close follow up for clinical changes and further next generation sequencing are crucial for definite diagnosis in neonates with encephalopathy of unclear cause. Frontiers Media S.A. 2023-08-08 /pmc/articles/PMC10442541/ /pubmed/37614902 http://dx.doi.org/10.3389/fped.2023.1155035 Text en © 2023 Thewamit, Khongkhatithum, Thampratankul, Kamolvisit, Khongkrapan and Wattanasirichaigoon. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Thewamit, Rapeepat Khongkhatithum, Chaiyos Thampratankul, Lunliya Kamolvisit, Wuttichart Khongkrapan, Arthaporn Wattanasirichaigoon, Duangrurdee Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
title | Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
title_full | Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
title_fullStr | Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
title_full_unstemmed | Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
title_short | Case report: Severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
title_sort | case report: severe nonketotic hyperglycinemia in a neonate without apparent seizures but concomitant cleft palate and cerebral sinovenous thrombosis |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442541/ https://www.ncbi.nlm.nih.gov/pubmed/37614902 http://dx.doi.org/10.3389/fped.2023.1155035 |
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