TY - JOUR
T1 - Non-ketotic hyperglycinemia
T2 - a life-threatening disorder in the neonate
AU - Tada, K.
AU - Kure, S.
AU - Takayanagi, M.
AU - Kume, A.
AU - Narisawa, K.
N1 - Funding Information:
This work was supported by grants from the Ministry of Education, Culture and from the Ministry of Health and Welfare, Japan.
PY - 1992
Y1 - 1992
N2 - Non-ketotic hyperglycinemia (NKH) is a well-recognized metabolic cause of life-threatening illness in the neonate. The fundamental defect is in the glycine cleavage enzyme (GCE), 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. In the majority of NKH patients in Finland, where there is a high incidence of NKH, it was found to be due to a common mutation - a point mutation resulting in amino acid alternation from Ser564 to Ile564. Prenatal diagnosis is possible by determining the activity of GCE and also by DNA analysis. Recent findings suggest that the high concentrations of glycine in the brain may contribute to the'pathophysiology of NKH by overactivating NMDA receptors via an action at the associated glycine modulatory site. These provide a possibility that early treatment with NMDA receptor antagonist may prevent brain damage in NKH.
AB - Non-ketotic hyperglycinemia (NKH) is a well-recognized metabolic cause of life-threatening illness in the neonate. The fundamental defect is in the glycine cleavage enzyme (GCE), 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. In the majority of NKH patients in Finland, where there is a high incidence of NKH, it was found to be due to a common mutation - a point mutation resulting in amino acid alternation from Ser564 to Ile564. Prenatal diagnosis is possible by determining the activity of GCE and also by DNA analysis. Recent findings suggest that the high concentrations of glycine in the brain may contribute to the'pathophysiology of NKH by overactivating NMDA receptors via an action at the associated glycine modulatory site. These provide a possibility that early treatment with NMDA receptor antagonist may prevent brain damage in NKH.
KW - glycine cleavage enzyme
KW - non-ketotic hyperglycinernia
KW - prenatal diagnosis
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U2 - 10.1016/0378-3782(92)90060-T
DO - 10.1016/0378-3782(92)90060-T
M3 - Article
C2 - 1396281
AN - SCOPUS:0026647178
VL - 29
SP - 75
EP - 81
JO - Screening
JF - Screening
SN - 0378-3782
IS - 1-3
ER -