Nonketotic hyperglycinemia (glycine encephalopathy): Laboratory diagnosis

Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of glyc ine metabolism caused by a defect in the glycine cleavage enzyme complex (G CS). GCS is a complex of four proteins encoded on four different chromosome s. In classical neonatal NKH, levels of cerebrospinal fluid (CSF) glycine a nd CSF/plasma glycine ratio are very high but the CSF results, in particula r, may be more difficult to interpret in later-onset, milder, or otherwise atypical NKH. Enzymatic confirmation of NKH requires a liver sample. Deline ation of which protein of the complex is defective is necessary to screen f or 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 s tage. Prenatal diagnosis by GCS assay in chorionic villus biopsies is not c ompletely reliable and will be replaced by molecular analysis in families w here the mutations are known. (C) 2001 Academic Press.