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Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues
Published on: May 26, 2018
IDH2 mutations in patients with D-2-hydroxyglutaric aciduria.
Martijn Kranendijk1, Eduard A Struys, Emile van Schaftingen
1Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, 1081 HV Amsterdam, Netherlands.
Science (New York, N.Y.)
|September 18, 2010
Summary
Germline mutations in IDH2 gene cause d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder. This discovery highlights the role of D-2-HG in metabolic diseases and cancer.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Somatic mutations in isocitrate dehydrogenase-1 and -2 (IDH1/IDH2) are linked to human cancers.
- These mutations alter enzyme function, leading to the production of D-2-hydroxyglutarate (D-2-HG).
Purpose of the Study:
- To investigate germline mutations in IDH2 associated with d-2-hydroxyglutaric aciduria (D-2-HGA).
Main Methods:
- Genetic analysis of 15 unrelated patients with D-2-HGA.
- Enzyme assays to assess IDH2 function.
Main Results:
- Identified heterozygous germline mutations in IDH2 in 15 patients with D-2-HGA.
- Confirmed mutations alter the Arg(140) residue in the IDH2 enzyme.
- Patients exhibited supraphysiological levels of D-2-HG.
Conclusions:
- Germline IDH2 mutations are a cause of D-2-HGA.
- D-2-HG accumulation is implicated in neurometabolic disorders.
- Further research into D-2-HG's role in metabolic disease and cancer is warranted.
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