Nonketotic hyperglycinemia (glycine encephalopathy). The primary disorder of glycine is a deficiency of the main catabolic enzyme, the glycine cleavage enzyme. Glycine is part of many biochemical pathways, but deficiency of the glycine cleavage enzyme removes the main catabolic breakdown of glycine resulting in increased levels of glycine. The disorder is known as nonketotic hyperglycinemia (NKH) or glycine encephalopathy. All forms of the disorder are characterized by cerebral dysfunction.
The glycine cleavage enzyme breaks glycine down into carbon dioxide and ammonia, and a methyl group is transferred to tetrahydrofolate creating methylene- tetrahydrofolate. The enzyme consists of four subunits: the P-protein (pyridoxalcontaining subunit), the H-protein (hydrogen carrier protein), the T-protein (tetrahydrofolate- requiring protein), and the l -protein (lipoamide dehydrogenase protein). The P-protein requires pyridoxal-phosphate, and disorders that affect the availability of pyridoxal- phosphate (such as PNPO ) result in secondary defi ciency of the enzyme activity. The H-protein is lipoylated and disorders in the biogenesis of the lipoylation result in variant forms of nonketotic hyperglycinemia.
Patients with NKH most often present neonatally in the first week of life (Hennermann et al. 2012 ). They develop lethargy, fail to feed, and progress to coma with frequent hiccupping and seizures. They have severe hypotonia. They often have a burst suppression pattern on EEG. These patients spontaneously recover from respiratory failure and regain spontaneous breathing within the first 3 weeks of life. Patients presenting during infancy have hypotonia, lethargy, and seizures (spasms or myoclonic seizures) with either multifocal epilepsy or hypsarrhythmia on EEG.
This text is an extract from “Physician´s Guide to the Diagnosis, Treatment and Follow-Up of Inherited Metabolic Diseases”, Editors: Nenad Blau, Marinus Duran, K. Michael Gibson, Carlos Dionisi-Vici, Publisher: Springer
Dinopoulos A, Matsubara Y, Kure S (2005) Atypical variants of nonketotic hyperglycinemia. Mol Genet Metab 86:61–69
Hennermann JB, Berger JM, Grieben U et al (2012) Prediction of longterm outcome in glycine encephalopathy: a clinical survey. J Inherit Metab Dis 35:253–261