Hyper-2-oxoglutaric aciduria in long-term mental handicap

One thousand one hundred and seventy-five mentally retarded patients in an institution (733 males and 442 females) were screened for urinary excretion of 2-oxoacids using a quantitative gas chromatographic method. On follow-up, in 10 out of 31 male patients with excretion of greater than or equal to 50 mmoles 2-oxoglutaric acid per mole creatinine, a previously unrecognized bacteriuria was considered the cause of hyper-2-oxoglutaric aciduria. Of the remaining 21, nine had elevated blood citric acid, and four had borderline elevations of blood pyruvic and/or 2-oxoglutaric acid. In the 11 males with persistent hyper-2-oxoglutaric aciduria an increased incidence of seizure disorders and cerebral palsy relative to the total patient population was found. Hyper-2-oxoglutaric aciduria with concomitant abnormalities of blood metabolites is thought to represent a heterogeneous group of mild inborn errors of energy metabolism which may be compatible with survival at least into young adulthood, but not with normal development of mental and neurological functions.