Atypical nonketotic hyperglycinemia with normal cerebrospinal fluid to plasma glycine ratio

The diagnosis of nonketotic hyperglycinemia is considered to depend upon th e presence of increased cerebrospinal fluid glycine and an increased cerebr ospinal fluid to plasma glycine ratio. We studied two siblings who have the neurologic and peripheral biochemical features of the atypical variant of nonketotic hyperglycinemia but have normal cerebrospinal fluid glycine and cerebrospinal fluid to plasma glycine ratios. The proband had reduced liver glycine cleavage system activity of 17% and 21% of mean normal values, con firmed in two independent laboratories. Her lymphoblast glycine cleavage sy stem activity was normal. Nonketotic hyperglycinemia can be present in the absence of increased cerebrospinal fluid glycine. Measurement of liver glyc ine cleavage system activity is indicated when nonketotic hyperglycinemia i s suggested by clinical features and peripheral glycine levels but cerebros pinal fluid glycine is normal.