2-Hydroxyglutaric Aciduria Panel

D-2-hydroxyglutaric aciduria (D2HGA) type 1 and type 2 are rare neurometabolic diseases associated with accumulation of D-2-hydroxyglutaric aciduria (D-2-HG) in urine. The cardinal clinical manifestations in both D2HGA subtypes are developmental delay, hypotonia and seizures. Age of onset is similar for both subtypes, typically occurring at 0-6 months of age in D2HGA type 1, and 0-2 years of age in D2HGA type 2. L-2-hydroxyglutaric aciduria (L2HGA) [OMIM #147920] is associated with accumulation of L-2-hydroxyglutaric aciduria in urine. L2HGA is a slowly progressive disorder with average age of onset of 2 years (range 0-7). The most commonly observed clinical features are developmental delay, epilepsy and cerebellar ataxia. Affected individuals with combined D-2 and L-2-hydroxyglutaric aciduria (D,L-2-HGA) typically have severe neonatal epileptic encephalopathy and absence of developmental progress. Death in the first year of life is common. 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. This panel includes sequence and deletion/duplication analysis of all the listed genes.