4 weeks
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Cultured Cells
Extracted DNA

Combined D-2 and L-2-hydroxyglutaric aciduria (D,L-2-HGA) [OMIM #615182] is a rare neurometabolic disease. Affected individuals typically have severe neonatal epileptic encephalopathy and absence of developmental progress. Death in the first year of life is common. Enlarged ventricles, subependymal pseudocysts, and delayed gyration and myelination are typical brain MRI findings in affected patients.

Homozygous and compound heterozygous mutations of the SLC25A1 gene [OMIM #190315] gene are associated with D,L-2-HGA. Missense, nonsense and frameshift mutations have been described. The SLC25A1 gene plays a role transporting citrate from the mitochondria to the cytosol, where it is converted into acetyl coenzyme A. Acetyl coenzyme-A is essential for fatty acid and sterol synthesis. Individuals with D,L-2-HGA have increased levels of both D-2 hydroxyglutaric acid and L-2 hydroxyglutaric acid in the urine. It is hypothesized that the increased excretion of these two compounds is related to impaired citrate transport from the mitochondria and disruption of the Krebs cycle caused by SLC25A1 mutations. Conventional urine organic acid screening with gas chromatography mass spectrometry (GC-MS) can detect increased 2-HG (2-hydroxyglutaric acid), but does not differentiate between enantiomeric D-2-HG and L-2-HG.