L-2-HYDROXYGLUTARIC ACIDURIA - 2 FURTHER CASES

L-2-Hydroxyglutaric aciduria is a rare organic aciduria associated with a neurological presentation. The first patient was described in 1980 by Duran et al. In 1988 Jaeken et al published a brief report on a second patient. Ten cases are known (Barth et al 1992); their clinical and neuroimaging similarities allow definition of a characteristic phenotype for a novel neurometabolic disease. The diagnosis depends upon the urinary organic acid profile. Routine gas chromatography-mass spectrometry (GC-MS) screening for organic acids reveals a large peak of 2-hydroxyglutaric acid (2-OH-glu). The absolute configuration of the acid should be determined as D-2-hydroxyglutaric aciduria and L-2-hydroxyglutaric aciduria are distinct diseases. D-2-Hydroxyglutaric aciduria was reported by Chalmers et al (1980) in a child with a protein-losing enteropathy without any neurological involvement. A second patient recently described by Gibson et al (1993) was a girl who presented with seizures, hypotonia, developmental delay and encephalopathy. In L-2-hydroxyglutaric aciduria the clinical presentation includes a progressive neurodegenerative disorder with magnetic resonance imaging suggestive of a spongiform encephalopathy. Concentrations of L-2-OH-glu in physiological fluids are: urines 200-4520 mmol/mol creatinine; plasma 7-60, mumol/L; CSF 40-500 mumol/L (control ranges are shown in Table 1). In both L- and D-2-hydroxyglutaric aciduria the primary defect is unknown. We report two new patients with L-2-hydroxyglutaric aciduria.