title: Successive distinct high-grade gliomas in L-2-hydroxyglutaric aciduria.
abstract: Patients with L-2-hydroxyglutaric aciduria are at risk for developing cerebral neoplasms, particularly gliomas, as one of the optical isomers of the known oncometabolite, 2-hydroxyglutarate is produced in L-2-hydroxyglutaric aciduria. To illustrate the concept of sustained oncogenic potential in permanent exposure to L-2-hydroxyglutarate in brain tissue, we present the medical history of a patient with L-2-hydroxyglutaric aciduria who underwent surgery to remove a right temporal anaplastic astrocytoma and developed an anatomically distinct, but histopathologically similar, tumor in the left frontal region 40 months later. This is the first reported case of successive distinct gliomas in a patient with L-2-hydroxyglutaric aciduria. While this implies a significant, cumulative lifetime risk for cerebral neoplasms in patients with this rare organic aciduria, it also allows further insight into a unique mechanism of tumorigenesis in the brain.
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital and Research Center, Memphis, TN, USA, zoltan.patay@stjude.org.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Patay
authors.forename: Brent A
authors.initials: BA
authors.lastname: Orr
authors.forename: Barry L
authors.initials: BL
authors.lastname: Shulkin
authors.forename: Scott N
authors.initials: SN
authors.lastname: Hwang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ying
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Boop
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D001254:Astrocytoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001706:Biopsy; D020739:Brain Diseases, Metabolic, Inborn / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005977:Glutarates / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D060787:Neoplasm Grading; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors