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CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 |
doi: 10.3389/fgene.2024.1432272
Unveiling Genetic and Phenotypic Variability in Nonketotic Hyperglycinemia: An Atypical Early Onset Case Associated with a Novel GLRX5 Variant
Provisionally accepted- 1 Service de Biochimie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
- 2 Hôpital Pédiatrique, Pôle Pédiatrique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
- 3 Service d'imagerie anténatale, de l'enfant et de la femme, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
- 4 Department of Medical Genetics, University of Bordeaux, MRGM INSERM U1211, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
- 5 Service de neurologie pédiatrique, CHU Bordeaux ; Univ. Bordeaux, CNRS, INCIA, UMR 5287, NRGen Team, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
Nonketotic hyperglycinemia (NKH) is a rare, autosomal recessive metabolic disorder usually associated with mutations in genes AMT, GLDC or GCSH involved in the glycine cleavage complex. Other genes have been linked with less severe NKH, associated with deficiency of lipoate cofactor such as GLRX5, LIAS, BOLA3.We identified a new case of GLRX5-mediated NKH who presented at 2-month with severe developmental delay and seizures. The initial suspicion was raised by the MRI and then confirmed by glycine measurements in cerebrospinal fluid and blood. Genetic analysis revealed a previously undescribed homozygous variant in the GLRX5 gene (NM_016417.3:c.367G>C; p.(Asp123His)). Despite medication and supportive care, he died at the age of 4 months after a sudden neurological deterioration. It was decided to limit therapeutic interventions due to the severity of the prognosis.The case was more severe than the previous GLRX5-mediated NKH described, regarding the early age at onset and the severity. Moreover, the genetic variant was located at a potentially crucial site for glutathione binding in the GLRX5 protein. This report, thereby, expands our understanding of NKH's genetic underpinnings and phenotypic variability, highlighting the crucial role of GLRX5 and other related genes in variant NKH.
Keywords: Nonketotic hyperglycinemia, NKH, GLRX5, glycine cleavage system, metabolic disorders, Clinical genetics
Received: 13 May 2024; Accepted: 23 Aug 2024.
Copyright: © 2024 Marin, Lebreton, Guibet, Mesli, Redonnet-Vernhet, Dexant, Lamireau, Roche, Gaschignard, Delmas, Margot and Bar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor 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.
* Correspondence:
Victor Marin, Service de Biochimie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
Louis Lebreton, Service de Biochimie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
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