Nonketotic hyperglycinemia (NKH) is a metabolic disorder with autosomal recessive inheritance, causing severe neurological symptoms. The metabolic lesion of NKH resides in the glycine cleavage system (GCS), a complex enzyme system with four components; P-,T-, H-, and L-protein. The enzymatic analysis revealed that more than 80% of the patients with NKH are deficient of P-protein activity. We cloned the P-protein cDNA and its genomic counterparts. P-protein gene spanned more than 130 kbp and had 25 exons. Several mutations were identified: One missence mutation accounts for 70% of the mutant alleles in Finland, where the incidence of NKH is unusually high. To elucidate the neuropathogenesis of NKH we examined structure and expression of the GCS in rat brain and primary cultured neurons and astrocytes. Those studies supports the hypothesis that the neurological disturbance in NKH is caused by excitoneurotoxicity through the NMDA receptor, which is allosterically activated by high concentration of glycine.
|Number of pages||1|
|Journal||Japanese Journal of Human Genetics|
|Publication status||Published - 1997|
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