Startseite Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye
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Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye

  • Ayşenur Engin Erdal ORCID logo EMAIL logo , Sümeyra Zeynep Özbey , Gülten Burcu Civelek Ürey , Aynur Küçükçongar Yavaş , Berrak Bilginer Gürbüz ORCID logo , Mehmet Gündüz , Esra Kiliç , Avni Merter Keçeli , Aydan Değerliyurt und Çiğdem Seher Kasapkara
Veröffentlicht/Copyright: 15. Juli 2025
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 38 Heft 9

Abstract

Objectives

L-2-hydroxyglutaric aciduria (L2HGA) is a hereditary metabolic disorder characterized by the accumulation of L-2-hydroxyglutaric acid in body fluids, particularly in cerebrospinal fluid, which disrupts neuron function in the central nervous system and triggers oxidative stress. It can cause seizures, developmental disorders, and behavioral abnormalities.

Methods

The study retrospectively evaluated the demographic information, initial symptoms, clinical characteristics, cranial magnetic resonance imaging (MRI) findings, and post-treatment biochemical changes of 10 cases diagnosed with L2HGA.

Results

The study included five paediatric and five adult cases with a molecular diagnosis of L2HGA. The mean age at diagnosis was 10.1 years. Convulsion was identified as the primary presenting symptom in 70 % of cases. We identified intellectual disability in 80 % of our cases. In addition to the classic cranial MRI findings of subcortical white matter involvement, basal ganglia involvement was detected in 60 % of cases. We found that 2-hydroxyglutaric acid levels in urine organic acid analysis were significantly decreased riboflavin and carnitine post-treatment, with a mean decrease of 133.89 ± 101.43 mmol/mol creatinine (p=0.017). The most common missense variant identified in the L2HGDH gene was c.905C>T (p.Pro302Leu), occurring at a frequency of 50 % (5/10). The cases did not report significant improvement in their symptoms with treatment.

Conclusions

L2HGA is a rare metabolic disorder that is more common in communities where consanguineous marriages are prevalent. Early diagnosis enables early treatment and protection of the brain from oxidative stress. As more cases are reported publicly, studies on genotype–phenotype relationships will yield more significant findings.

Keywords: cerebral organic acidemia; L-2-hydroxyglutaric aciduria; L2HGDH ; movement disorder; intellectual disability
Corresponding author: Dr. Ayşenur Engin Erdal, Department of Pediatric Metabolic Diseases, Ankara Bilkent City Hospital, Ankara, 06800, Türkiye, E-mail:

Acknowledgement

We greatly appreciate our patients and family’s cooperation.

  1. Research ethics: The study was carried out in compliance with the principles outlined in the Declaration of Helsinki. We obtained approval for our study from the local ethics committee of our hospital (Ankara Bilkent City Hospital No. 2 Clinical Research Ethics Committee file number: E2-24-6476). Our study was conducted in accordance with the Helsinki Declaration (as revised in 2013).

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. AEE, ÇSK: the study’s design and writing. SZÖ, GBCÜ, AKY, BBG, MG: following the patients and collecting data. EK: the assessing the results of the genetic analysis. AMK: evaluating the neuroimaging results. AD: the neurological follow-up and evaluation of the EEG results.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This research did not receive any financial or sponsorship support.

  7. Data availability: The raw data can be obtained on request from the corresponding author.

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Received: 2025-01-09
Accepted: 2025-07-06
Published Online: 2025-07-15
Published in Print: 2025-09-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Mini Review
  3. Transition of care from childhood/adolescence to adulthood in familial hypercholesterolemia
  4. Original Articles
  5. Performance of adult height prediction methods in 6 to 8-year-old girls with GnRH-dependent precocious puberty
  6. Height velocity in the detection of growth disorders reconsidered: a retrospective analysis of the DONALD study
  7. Differentiating transient and permanent congenital hypothyroidism: predictive clues from Istanbul, Türkiye
  8. Evaluation of thyrotrophic and lactotrophic reserves in patients with pituitary dwarfism with and without empty sella turcica
  9. Exploring the impact of androgen levels on depression and anxiety in adolescent females: a clinical perspective
  10. The diagnostic value of stimulated androgen ratios in 5-alpha reductase type 2 (SRD5A2) deficiency: a case series and review of the literature
  11. Prolonged symptom duration and the potential for gradual progression in pediatric adrenocortical tumors: observations from the MET studies
  12. Distinguishing organic from idiopathic central precocious puberty: clinical characteristics and predictive factors for organic etiology in a multicenter Italian cohort study
  13. Endocrinopathies associated with pediatric common variable immunodeficiency
  14. Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye
  15. Short Communications
  16. Stress hyperglycemia in pediatric patients as a risk factor for type 1 diabetes – a single center experience
  17. Observations of the effect of gonadotropin-releasing hormone analog treatment on psychosocial well-being in transgender youth and their caregivers – a pilot study
  18. Letter to the Editor
  19. GNB1 haploinsufficiency presents as monogenic obesity syndrome
  20. Case Reports
  21. Rare pediatric insulinoma case diagnosed by endoscopic ultrasonography: insights into endogenous hyperinsulinemic hypoglycemia
  22. Caudal epidural steroid injection as a novel therapy for treatment-induced neuropathy of diabetes in children: report of two cases
  23. A novel homozygous missense DNAJC3 variant in syndromic juvenile-onset diabetes
  24. 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: case report of a child with rare HMGCL gene variants
https://doi.org/10.1515/jpem-2025-0021
Schlagwörter für diesen Artikel
cerebral organic acidemia; L-2-hydroxyglutaric aciduria; L2HGDH; movement disorder; intellectual disability

Artikel in diesem Heft

  1. Frontmatter
  2. Mini Review
  3. Transition of care from childhood/adolescence to adulthood in familial hypercholesterolemia
  4. Original Articles
  5. Performance of adult height prediction methods in 6 to 8-year-old girls with GnRH-dependent precocious puberty
  6. Height velocity in the detection of growth disorders reconsidered: a retrospective analysis of the DONALD study
  7. Differentiating transient and permanent congenital hypothyroidism: predictive clues from Istanbul, Türkiye
  8. Evaluation of thyrotrophic and lactotrophic reserves in patients with pituitary dwarfism with and without empty sella turcica
  9. Exploring the impact of androgen levels on depression and anxiety in adolescent females: a clinical perspective
  10. The diagnostic value of stimulated androgen ratios in 5-alpha reductase type 2 (SRD5A2) deficiency: a case series and review of the literature
  11. Prolonged symptom duration and the potential for gradual progression in pediatric adrenocortical tumors: observations from the MET studies
  12. Distinguishing organic from idiopathic central precocious puberty: clinical characteristics and predictive factors for organic etiology in a multicenter Italian cohort study
  13. Endocrinopathies associated with pediatric common variable immunodeficiency
  14. Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye
  15. Short Communications
  16. Stress hyperglycemia in pediatric patients as a risk factor for type 1 diabetes – a single center experience
  17. Observations of the effect of gonadotropin-releasing hormone analog treatment on psychosocial well-being in transgender youth and their caregivers – a pilot study
  18. Letter to the Editor
  19. GNB1 haploinsufficiency presents as monogenic obesity syndrome
  20. Case Reports
  21. Rare pediatric insulinoma case diagnosed by endoscopic ultrasonography: insights into endogenous hyperinsulinemic hypoglycemia
  22. Caudal epidural steroid injection as a novel therapy for treatment-induced neuropathy of diabetes in children: report of two cases
  23. A novel homozygous missense DNAJC3 variant in syndromic juvenile-onset diabetes
  24. 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: case report of a child with rare HMGCL gene variants
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