Recent study on nonketotic hyperglycinemia, an inborn error of glycine metabolism, is reviewed from clinical, metabolic, molecular, and neuropathological points of view. This disorder is caused by an inherited deficiency of the mitochondrial glycine cleavage system (GCS), which causes accumulation of glycine in such body fluids as plasma, cerebrospinal fluid, and urine. There are four disease types: neonatal, infantile, late-onset, and transient types. The genetic backgrounds of the neonatal and infantile types have been largely clarified by a comprehensive mutational screening of genes encoding three components of the GCS, while the molecular pathogenesis of the late-onset and transient types are largely unknown. In the central nervous system of vertebrates, the GCS has been identified in astrocytes and neural stem cells. The GCS in astrocytes is co-localized with N-methyl-D-aspartate receptors, and is thought to maintain the glycine level around the receptors, while the physiological and pathological roles of the GCS in neural stem cells remains to be elucidated.


(Communicated by Tamio YAMAKAWA, M.J.A.)