Nonketotic hyperglycinemia. Molecular lesion and pathophysiology

K. Tada, Shigeo Kure

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)


Nonketotic hyperglycinemia (NKH) is an autosomal recessive metabolic disorder caused by the defect in the glycine cleavage system (GCS), which consists of four protein components. Our study revealed that the majority of NKH patients had a specific defect in P-protein (glycine decarboxylase). The primary lesion of NKH in gene level was investigated, using cDNA encoding human glycine decarboxylase. A three-base deletion, resulting in deletion of Phe756, was found in a Japanese patient with NKH. The majority of NKH patients in Finland, where there is a high incidence of NKH. was found to be due to a common mutation, a point mutation resulting in the amino acid alternation from Ser564 to Ile64 Prenatal diagnosis is feasible by determining the activity of GCS and is also possible by DNA analysis. Recent findings suggest that a high concentrations of glycine in the brain may contribute to the pathophysiology of NKH by overactivating N-methyl-D-aspartate (NMDA) receptors allosterically, which may result in intracellular calcium accumulation, DNA fragmentation and neuronal death. These provide a possibility that the early treatment with NMDA receptor antagonist may prevent the brain damage in NKH.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalInternational Pediatrics
Issue number1
Publication statusPublished - 1993 Jan 1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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