Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis.
Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of glycine metabolism caused by a defect in the glycine cleavage enzyme complex (GCS). GCS is a complex of four proteins encoded on four different chromosomes. In classical neonatal NKH, levels of cerebrospinal fluid (CSF) glycine and CSF/plasma glycine ratio are very high but the CSF results, in particular, may be more difficult to interpret in later-onset, milder, or otherwise atypical NKH. Enzymatic confirmation of NKH requires a liver sample. Delineation of which protein of the complex is defective is necessary to screen for mutations in the appropriate gene. Except for Finnish NKH patients, few recurrent mutations have yet been found, although analysis of the P-protein gene (the site of the defect in the majority of patients) is at an early stage. Prenatal diagnosis by GCS assay in chorionic villus biopsies is not completely reliable and will be replaced by molecular analysis in families where the mutations are known.
Applegarth
D A
DA
Department of Pediatrics, University of British Columbia, 4480 Oak Street, Vancouver, V6H 3V4, British Columbia. applegar@interchange.ubc.ca
Toone
J R
JR
D000818:Animals; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D006580:Genetic Carrier Screening; D005998:Glycine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D020158:Hyperglycinemia, Nonketotic / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods
D005998:Glycine