RARE DISEASE
2-hydroxyglutaric aciduria
2-hydroxyglutaric aciduria
2-hydroxyglutaric aciduria
Synonyms: 2-hydroxyglutaric acidemia
Synonyms: 2-hydroxyglutaric acidemia
Synonyms: 2-hydroxyglutaric acidemia
Drug discovery
0
drugs
With orphan designations
Overview
2-hydroxyglutaric aciduria encompasses three rare neurometabolic disorders (D-2, L-2, and combined D,L-2-hydroxyglutaric aciduria) caused by defects in mitochondrial enzymes or IDH2 mutations [1][3][14]. These autosomal recessive conditions (except D-2 type II, which is dominant) feature progressive cerebral damage, with symptoms including developmental delay, seizures, hypotonia, ataxia, and characteristic MRI findings (subcortical leukoencephalopathy in L-2-HGA; delayed cerebral maturation/ependymal cysts in D-2-HGA) [1][3][6][7]. Diagnosis relies on chiral urinary organic acid analysis and genetic testing [3][14].
Categories: rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases
Research Papers
73 drug discovery papers about 2-hydroxyglutaric aciduria, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
73 drug discovery papers about 2-hydroxyglutaric aciduria, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-04-28 | Metformin-NAD+ Precursor Combination for 2-HG Detoxification
Metformin activates AMPK-mediated enhancement of 2-hydroxyglutarate dehydrogenase expression while nicotinamide riboside supplementation provides cofactor support for the NAD+-dependent enzymatic clearance of accumulated 2-HG. This combination addresses both enzyme insufficiency and cofactor depletion in 2-hydroxyglutaric aciduria.
2026-01-14 | Early manifestations of D-2-hydroxyglutaric aciduria type II
D-2-hydroxyglutaric aciduria type II (ICD-10 code E72.8: Other specified disorders of amino-acid metabolism, ОMIM #613657) is a rare neurometabolic disorder associated with a pathogenic mutation in the IDH2 gene, which encodes a mitochondrial enzyme called isocitrate dehydrogenase 2. The pathogenesis of the disease is based on the accumulation of neurotoxic and cytotoxic 2-hydroxyglutarate in the body fluids, leading to the development of characteristic clinical manifestations. These include neurological disorders and eye conditions, hypotonia, neurodevelopmental delay, seizures, and cardiomyopathy. D-2-hydroxyglutaric aciduria type II has not been sufficiently studied. Despite the introduction of many metabolic disorders in expanded newborn screening, including glutamic acidemias, which are similar in name and course, this disease is still diagnosed only with the help of special biochemical and molecular genetic tests. This article presents early manifestations, developmental characteristics, neuropsychological and infectious status in a child with D-2-hydroxyglutaric aciduria. Key words: D-2-hydroxyglutaric aciduria type II, D-2-hydroxyglutarate, IDH2 gene, epilepsy, cardiomyopathy, infectious process, developmental delay, hypoxic-ischemic encephalopathy, floppy infant syndrome
2026-01-14 | 2-hydroxyglutaric aciduria in the practice of neonatologists and pediatricians: possibilities for early diagnosis and treatment
2-hydroxyglutaric aciduria (ICD-10 code E72.8: Other specified disorders of amino-acid metabolism) is a group of rare metabolic disorders resulting from the accumulation of α-ketoglutarate derivatives in mitochondria: D- and L-enantiomers of 2-hydroxyglutaric acid. This pathology is caused by a wide range of mutations in the genes of mitochondrial enzymes, which explains the existence of several subtypes of the disease in the described group. Over the 45 years since the first mention of 2-hydroxyglutaric aciduria, nearly 500 cases have been reported worldwide. 2-hydroxyglutaric aciduria leads to multisystemic disorders, primarily neurological, severe disability, or death, which determines the importance of early diagnosis. The disease is not included in neonatal screening, but certain similarities between its clinical and laboratory manifestations and various acidemias and other metabolic disorders, as well as their severe consequences and outcomes, necessitate further study and systematization of knowledge about this pathology. This article describes current approaches to the diagnosis and treatment of 2-hydroxyglutaric aciduria in newborns and young children. Key words: inherited metabolic disorders, aciduria, 2-hydroxyglutaric acid, 2-hydroxyglutaric aciduria, D-2-hydroxyglutaric aciduria types I and II, L-2-hydroxyglutaric aciduria
2025-12-25 | Successful Treatment of 2-hydroxyglutaric Aciduria Diagnosed in Adulthood, Three Decades After the Onset: A Case Report and Literature Review.
2-Hydroxyglutaric aciduria is a rare genetic metabolic disorder, especially in Japan. Although magnetic resonance images show characteristic abnormalities in the subcortical white matter, some cases have been diagnosed in adulthood, namely many decades after onset. We herein report the case of a bedridden 37-year-old 2-hydroxyglutaric aciduria male patient who was diagnosed three decades after onset. Despite this, combination treatment with riboflavin and levocarnitine improved his condition, thus allowing him to walk by himself. Considering our case and the previous literature, we emphasize the importance of correctly diagnosing and treating patients with 2-hydroxyglutaric aciduria.
2025-06-04 | L‐2‐Hydroxyglutaric Aciduria Complicated by Cerebral Neoplasm
Data S1. Investigations of index patient. MRI (magnetic resonance imaging) brain of the index patient at the age of 15 years. Genetic report of the index patient. Data S2. Summary and neuroimaging of the affected younger sibling. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
small molecules
2026-04-28 | Metformin-NAD+ Precursor Combination for 2-HG Detoxification
Metformin activates AMPK-mediated enhancement of 2-hydroxyglutarate dehydrogenase expression while nicotinamide riboside supplementation provides cofactor support for the NAD+-dependent enzymatic clearance of accumulated 2-HG. This combination addresses both enzyme insufficiency and cofactor depletion in 2-hydroxyglutaric aciduria.
2026-01-14 | Early manifestations of D-2-hydroxyglutaric aciduria type II
D-2-hydroxyglutaric aciduria type II (ICD-10 code E72.8: Other specified disorders of amino-acid metabolism, ОMIM #613657) is a rare neurometabolic disorder associated with a pathogenic mutation in the IDH2 gene, which encodes a mitochondrial enzyme called isocitrate dehydrogenase 2. The pathogenesis of the disease is based on the accumulation of neurotoxic and cytotoxic 2-hydroxyglutarate in the body fluids, leading to the development of characteristic clinical manifestations. These include neurological disorders and eye conditions, hypotonia, neurodevelopmental delay, seizures, and cardiomyopathy. D-2-hydroxyglutaric aciduria type II has not been sufficiently studied. Despite the introduction of many metabolic disorders in expanded newborn screening, including glutamic acidemias, which are similar in name and course, this disease is still diagnosed only with the help of special biochemical and molecular genetic tests. This article presents early manifestations, developmental characteristics, neuropsychological and infectious status in a child with D-2-hydroxyglutaric aciduria. Key words: D-2-hydroxyglutaric aciduria type II, D-2-hydroxyglutarate, IDH2 gene, epilepsy, cardiomyopathy, infectious process, developmental delay, hypoxic-ischemic encephalopathy, floppy infant syndrome
2026-01-14 | 2-hydroxyglutaric aciduria in the practice of neonatologists and pediatricians: possibilities for early diagnosis and treatment
2-hydroxyglutaric aciduria (ICD-10 code E72.8: Other specified disorders of amino-acid metabolism) is a group of rare metabolic disorders resulting from the accumulation of α-ketoglutarate derivatives in mitochondria: D- and L-enantiomers of 2-hydroxyglutaric acid. This pathology is caused by a wide range of mutations in the genes of mitochondrial enzymes, which explains the existence of several subtypes of the disease in the described group. Over the 45 years since the first mention of 2-hydroxyglutaric aciduria, nearly 500 cases have been reported worldwide. 2-hydroxyglutaric aciduria leads to multisystemic disorders, primarily neurological, severe disability, or death, which determines the importance of early diagnosis. The disease is not included in neonatal screening, but certain similarities between its clinical and laboratory manifestations and various acidemias and other metabolic disorders, as well as their severe consequences and outcomes, necessitate further study and systematization of knowledge about this pathology. This article describes current approaches to the diagnosis and treatment of 2-hydroxyglutaric aciduria in newborns and young children. Key words: inherited metabolic disorders, aciduria, 2-hydroxyglutaric acid, 2-hydroxyglutaric aciduria, D-2-hydroxyglutaric aciduria types I and II, L-2-hydroxyglutaric aciduria
2025-12-25 | Successful Treatment of 2-hydroxyglutaric Aciduria Diagnosed in Adulthood, Three Decades After the Onset: A Case Report and Literature Review.
2-Hydroxyglutaric aciduria is a rare genetic metabolic disorder, especially in Japan. Although magnetic resonance images show characteristic abnormalities in the subcortical white matter, some cases have been diagnosed in adulthood, namely many decades after onset. We herein report the case of a bedridden 37-year-old 2-hydroxyglutaric aciduria male patient who was diagnosed three decades after onset. Despite this, combination treatment with riboflavin and levocarnitine improved his condition, thus allowing him to walk by himself. Considering our case and the previous literature, we emphasize the importance of correctly diagnosing and treating patients with 2-hydroxyglutaric aciduria.
2025-06-04 | L‐2‐Hydroxyglutaric Aciduria Complicated by Cerebral Neoplasm
Data S1. Investigations of index patient. MRI (magnetic resonance imaging) brain of the index patient at the age of 15 years. Genetic report of the index patient. Data S2. Summary and neuroimaging of the affected younger sibling. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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0 orphan drug designations.
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