ABSTRACT
L-2-hydroxyglutaric aciduria was first described by M. Duran and colleagues in 1980 in a five-year-old Moroccan boy with psychomotor impairment. A brain tumor was found in a 17-year-old boy with L-2-hydroxyglutaric aciduria, and seven other patients have been identified with brain tumors, suggesting an increased risk. Like D-2-hydroxyglutaric acid, L-2-hydroxyglutaric is a waste product of the tricyclic acid cycle without metabolic function, and accumulation of these acids has toxic effects. L-2-hydroxyglutaric acid is found in increased concentrations in the urine, blood, and cerebrospinal fluid. In addition, a number of hydroxydicarboxylic acids were probably only found elevated in cerebrospinal fluid because of intracerebral generation of 2-hydroxyglutaric and 2,4-hydroxyglutaric acids and trapping of other dicarboxylic acids sharing the same transporter. Missense mutations changed strictly conserved or semiconserved amino acid residues with very different size or polarity.
