TY - JOUR
T1 - Two novel laboratory tests facilitating diagnosis of glycine encephalopathy (nonketotic hyperglycinemia)
AU - Kure, Shigeo
N1 - Funding Information:
We are grateful to the families who participated in this study. This work was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology in Japan, and a grant from the Ministry of Health, Labor, and Public Welfare in Japan.
PY - 2011/10
Y1 - 2011/10
N2 - Glycine encephalopathy (GE), also known as non-ketotic hyperglycinemia, is a life-threatening metabolic disease caused by inherited deficiency of the glycine cleavage system (GCS). GE is characterized by accumulation of a large amount of glycine in serum and cerebrospinal fluids. In typical cases with GE, coma, profound hypotonia, and intractable seizures develop within several days of life. Patients with atypical symptoms may have delayed or missed diagnosis because of non-specific symptoms. It is sometimes problematic to confirm the diagnosis of GE since it requires either invasive liver biopsy for measurement of GCS activity or exhaustive mutational screening of three GCS genes, GLDC, AMT, and GCSH. We herein describe two novel laboratory tests for diagnosis of GE, [1- 13C]glycine breath test and the multiplex ligation-dependent probe amplification (MLPA) for detection of large deletions in GLDC. The [1- 13C]glycine breath test has been developed for noninvasive enzymatic diagnosis of GE. Because the GCS generates CO 2 by degradation of glycine, the GCS activity could be evaluated in vivo by measurement of exhaled 13CO 2 after administration of a stable isotope, [1- 13C]glycine. The MLPA has been developed for improvement in mutation detection rate in GE: Deletions involving multiple GDLC exons are prevalent among GE patients, but cannot be detected by the exon-sequencing analysis. Two novel diagnosis methods would facilitate diagnosis of hyperglycinemic patients as having GE.
AB - Glycine encephalopathy (GE), also known as non-ketotic hyperglycinemia, is a life-threatening metabolic disease caused by inherited deficiency of the glycine cleavage system (GCS). GE is characterized by accumulation of a large amount of glycine in serum and cerebrospinal fluids. In typical cases with GE, coma, profound hypotonia, and intractable seizures develop within several days of life. Patients with atypical symptoms may have delayed or missed diagnosis because of non-specific symptoms. It is sometimes problematic to confirm the diagnosis of GE since it requires either invasive liver biopsy for measurement of GCS activity or exhaustive mutational screening of three GCS genes, GLDC, AMT, and GCSH. We herein describe two novel laboratory tests for diagnosis of GE, [1- 13C]glycine breath test and the multiplex ligation-dependent probe amplification (MLPA) for detection of large deletions in GLDC. The [1- 13C]glycine breath test has been developed for noninvasive enzymatic diagnosis of GE. Because the GCS generates CO 2 by degradation of glycine, the GCS activity could be evaluated in vivo by measurement of exhaled 13CO 2 after administration of a stable isotope, [1- 13C]glycine. The MLPA has been developed for improvement in mutation detection rate in GE: Deletions involving multiple GDLC exons are prevalent among GE patients, but cannot be detected by the exon-sequencing analysis. Two novel diagnosis methods would facilitate diagnosis of hyperglycinemic patients as having GE.
KW - 13C-glycine breath test
KW - Decarboxylation of glycine in vivo
KW - Detection of large deletions in GLDC
KW - The MLPA analysis
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U2 - 10.1016/j.braindev.2011.03.001
DO - 10.1016/j.braindev.2011.03.001
M3 - Review article
C2 - 21470805
AN - SCOPUS:80052504965
VL - 33
SP - 753
EP - 757
JO - Brain and Development
JF - Brain and Development
SN - 0387-7604
IS - 9
ER -