Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder due to a fundamental defect in the glycine cleavage system, which leads to neuronal dysfunction caused by two receptor-mediated mechanisms. It is a life-threatening condition in the neonate. Until now, the disease has not been described from Saudi Arabia. We report on three Saudi newborns (two males and one female) who had NKH. Two of these were siblings (male and female). Following uneventful deliveries, they presented between the first and third day of lift with progressive lethargy, poor feeding, recurrent apnea and severe hypotonia. Two newborns had myoclonic seizures, whereas electroencephalogram showed burst-suppression pattern in ail of them. The diagnosis was confirmed by high cerebrospinal fluid/plasma glycine ratio (0.2 and 1.08) in two patients (normal < 0.03), whereas a sibling of one uf the neonates had a high glycine level. Both siblings died during the second month of life despite therapy with dextromethorphan (an N-methyl-D-aspartate [NMDA] receptor antagonist) in one of them. The third baby had ketamine (noncompetitive NMDA receptor antagonist) and sodium benzoate (that conjugates with glycine, forming nontoxic hippuric acid). Although his seizures were controlled, he survived with severe neurological sequelae.
