Characteristics of glioma in L-2-Hydroxyglutaric Aciduria: a case report and literature review
Abstract
INTRODUCTION: In IDH-mutant gliomas, the accumulation of 2-hydroxyglutarate (2-HG) induces widespread epigenetic disruption and drives gliomagenesis. L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disorder causing L-2-HG accumulation, resulting in myelin toxicity, and increased brain tumor risk. Gliomas arising in L-2-HGA remain poorly characterized. We report a new case of high-grade glioma in a L-2-HGA patient, including methylome profiling, and review previously published cases to clarify glioma characteristics and provide hypothesis regarding 2-HG-driven gliomagenesis. MATERIAL AND METHODS: A new case of high-grade glioma in a L-2-HGA patient was locally identified. A literature review was conducted following PRISMA guidelines. RESULTS: A 45-year-old L-2-HGA woman developed a diffuse anaplastic glioma harboring a TERTp C228T mutation, revealed by progressive neurological decline. Methylation profiling assigned the tumor to the "Diffuse pediatric-type high-grade gliomas" superfamily (score ≥0.9). Despite chemotherapy, the patient died 5 months post-diagnosis. Literature review yielded 20 documented cases of glioma in L-2-HGA patients, with a mean age at diagnosis of 18 ± 9.5 years. Tumor location was relatively stereotyped, with 75% in the temporal lobe or thalamus/basal ganglia. Molecular alterations typical of glioblastoma were observed (EGFR amplification, partial 10q loss) and the epigenetic profile was similar. Although some tumors misleadingly harbored the microscopic features of low-grade gliomas, the median overall survival was 6 months. CONCLUSION: Although gliomas associated with L-2HGA predominantly affect young patients, their characteristics differ from those of IDH-mutant gliomas. These tumors may possibly be related to diffuse pediatric-type high-grade glioma H3-wildtype and IDH-wildtype, which is consistent with their highly aggressive clinical course.
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BibTeX
@article{lutz2026characteristics,
title = {{Characteristics of glioma in L-2-Hydroxyglutaric Aciduria: a case report and literature review}},
author = {Carmen Lutz and Marc Barritault and Alexandre Vasiljevic and Serkan Cakmak and Alexis Chambost and Alexandre Bani-Sadr and Clémentine Gallet and David Meyronet and Francois Ducray and Thiebaud Picart},
journal = {Neurochirurgie},
year = {2026},
month = oct,
doi = {10.1016/j.neuchi.2026.101869},
url = {https://hal.science/hal-05837537v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Characteristics of glioma in L-2-Hydroxyglutaric Aciduria: a case report and literature review
AU - Carmen Lutz
AU - Marc Barritault
AU - Alexandre Vasiljevic
AU - Serkan Cakmak
AU - Alexis Chambost
AU - Alexandre Bani-Sadr
AU - Clémentine Gallet
AU - David Meyronet
AU - Francois Ducray
AU - Thiebaud Picart
PY - 2026
DA - 2026/10/23
JO - Neurochirurgie
DO - 10.1016/j.neuchi.2026.101869
UR - https://hal.science/hal-05837537v1
AB - INTRODUCTION: In IDH-mutant gliomas, the accumulation of 2-hydroxyglutarate (2-HG) induces widespread epigenetic disruption and drives gliomagenesis. L-2-hydroxyglutaric aciduria (L-2-HGA) is a metabolic disorder causing L-2-HG accumulation, resulting in myelin toxicity, and increased brain tumor risk. Gliomas arising in L-2-HGA remain poorly characterized. We report a new case of high-grade glioma in a L-2-HGA patient, including methylome profiling, and review previously published cases to clarify glioma characteristics and provide hypothesis regarding 2-HG-driven gliomagenesis. MATERIAL AND METHODS: A new case of high-grade glioma in a L-2-HGA patient was locally identified. A literature review was conducted following PRISMA guidelines. RESULTS: A 45-year-old L-2-HGA woman developed a diffuse anaplastic glioma harboring a TERTp C228T mutation, revealed by progressive neurological decline. Methylation profiling assigned the tumor to the "Diffuse pediatric-type high-grade gliomas" superfamily (score ≥0.9). Despite chemotherapy, the patient died 5 months post-diagnosis. Literature review yielded 20 documented cases of glioma in L-2-HGA patients, with a mean age at diagnosis of 18 ± 9.5 years. Tumor location was relatively stereotyped, with 75% in the temporal lobe or thalamus/basal ganglia. Molecular alterations typical of glioblastoma were observed (EGFR amplification, partial 10q loss) and the epigenetic profile was similar. Although some tumors misleadingly harbored the microscopic features of low-grade gliomas, the median overall survival was 6 months. CONCLUSION: Although gliomas associated with L-2HGA predominantly affect young patients, their characteristics differ from those of IDH-mutant gliomas. These tumors may possibly be related to diffuse pediatric-type high-grade glioma H3-wildtype and IDH-wildtype, which is consistent with their highly aggressive clinical course.
SN - 0028-3770
SN - 1773-0619
ER -