2-Hydroxyglutaric Aciduria. L-2-Hydroxyglutaric aciduria. L-2-Hydroxyglutaric acid dehydrogenase deficiency.
Incidence
AR disease. More than 106 patients described.
Clinical Characteristics
Onset is insidious between 6 and 10 years. It is slowly progressive. There is progressive cerebellar ataxia in 80-100% of cases, moderate to severe mental retardation and developmental delay (mental and motor delay) in almost all cases. mild dystonic and extrapyramidal signs in 30-40%, stunting of growth, some pyramidal signs present, epileptic seizures occur in 50-70% of cases, dysarthria, macrocephaly in 50%. Hypotonia is present in early stages and spasticity later on. Many patients remain undiagnosed until adolescence or even adulthood. MRI shows cerebellar atrophy, lesions in the subcortical white matter and abnormal signals in the dentate nuclei, caudate nucleus, globus pallidus and putamen. As the disease progresses, abnormalities of white matter and basal ganglia signal intensities become more diffuse, followed by cerebral white matter atrophy. The disease has a protracted course extending well into adolescence or adulthood. In 25% of cases some neurological decompensation or regression occur. It may be an association of L-2-HGA with CNS tumors.
Precipitants
no
Provocation Tests
none
Diagnostic Procedures
EB-L, Lysine increased in plasma and CSF. - GC/MS in urine shows elevated 2-OH-glutaric acid. Although the clinical presentation often can suggest either D-2-HGA or L-2-HGA, chiral differentiation performed with GC-MS or liquid chromatography-tandem mass spectrometry (LC-MS/MS) is mandatory for the correct differential diagnosis.