The enzymatic defect causing this progressive
neurometabolic disorders is yet to be found. l-2-Hydroxyglutaric acid
is a stereoisomer of d-2-hydroxyglutaric acid. Elevated levels of l-2-hydroxyglutaric acid are found in the urine, cerebrospinal fluid (CSF),
and, to a lesser degree, in the serum. Plasma and CSF levels of lysine are
elevated in some of these patients. In most patients, the initial symptoms
are a delay of speech, unsupported walk and febrile seizures within the first
2 years of life. Over the following years, mental retardation associated to
cerebellar ataxia with or without dystonia, pyramidal signs, and seizures
develop. However, onset can be as early as neonatal age or as late as
adolescent age. The oldest patient reported with this disorder was 57 years
old. MRI scans reveal a consistent pattern with symmetrical subcortical
leukoencephalopathy and cerebellar atrophy (vermis more than hemispheres).
Furthermore, pathologic changes can—although inconsistently—be detected
in the dentate nuclei, putamina, and globus pallidus.