Page 97 - BH-2-3

Brain & Heart

CASE REPORT
L2-hydroxyglutaric aciduria presenting with

learning disability and cerebellar signs: A case
report

Maththage H. K. Amarasekara *, Arndt Rolfs , Christian Beetz ,
1
2
2
2
Sabine Schroder , Ranawaka Arachchige S. R. Gunasekara , Pyara Rathnayake ,
4
3
and Eresha Jasinge 5
1 Department of Chemical Pathology, District General Hospital, Monaragala, Sri Lanka
2 CENTOGENE GmbH, Am Strande 7, Rostock, Germany
3 Department of Chemical Pathology, Apeksha Hospital, Maharagama, Sri Lanka
4 Department of Paediatric Neurology, Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka
5 Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo 8, Sri Lanka

Abstract

L-2-hydroxyglutaric aciduria (L2HGA) is a rare, autosomal recessive neurometabolic
disorder due to variants in the L2HGDH gene, which encodes L-2-hydroxyglutarate
dehydrogenase (L2HGDH), an enzyme involved in tricarboxylic acid cycle. Deficiency
of L2HGDH causes leukoencephalopathy predominantly affecting the cerebellum.
This case presents L2HGA in a 12-year-old Sri Lankan boy born to third-degree
consanguineous parents, who also showed learning disability and bilateral
cerebellar signs. Magnetic resonance imaging (MRI) of the brain revealed T2/FLAIR
*Corresponding author:
Maththage H. K. Amarasekara hyperintensities in bilateral symmetrical subcortical white matter involving the
(m29847@pgim.cmb.ac.lk) cerebellum. A diagnosis of 2-hydroxyglutaric aciduria was made after a massive
peak of 2-hydroxyglutaric acid (2HG) was observed in the analysis of urine organic
Citation: Amarasekara
MHK, Rolfs A, Beetz C, et al. acids (UOA) using gas chromatography/mass spectrometry. Genetic variant analysis
L2-hydroxyglutaric aciduria revealed two heterozygous pathogenic variants in the L2HGDH gene, confirming
presenting with learning disability the genetic diagnosis of autosomal recessive L2HGA. Parental genetic testing
and cerebellar signs: A case report.
Brain & Heart. 2024;2(3):2145. confirmed the trans phase of the variants in the index patient and their carrier status
doi: 10.36922/bh.2145 of a pathogenic L2HGDH variant. Despite typical clinical features and classical MRI
Received: October 31, 2023 findings, initial clues toward the diagnosis are mainly derived from the UOA analysis.
In conclusion, this case underscores the paramount importance of analyzing the
Accepted: March 13, 2024
UOA profile in the process of identifying rare metabolic causes, such as L2HGA, that
Published Online: August 22, 2024 contribute to learning disability with neurological involvement in children.
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the Keywords: L2-hydroxyglutaric aciduria; Urine organic acids; Gas chromatography/mass
Creative Commons Attribution spectrometry
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited.
1. Background
Publisher’s Note: AccScience
Publishing remains neutral with 2-hydroxyglutaric aciduria (2HGA) is a rare autosomal recessive neurometabolic
regard to jurisdictional claims in 1
published maps and institutional disorder characterized by slow progression. Since the first description of this disorder
2
affiliations. by Duran et al., up to 300 cases have been reported worldwide thus far. 1

Volume 2 Issue 3 (2024) 1 doi: 10.36922/bh.2145