Nonketotic hyperglycinemia, also known as glycine encephalopathy, is a genetic disorder distinguished by the accumulation of glycine in body tissues. The condition is either fatal or presents with several mental and neurological disability in early life. Only a minority of patients develop a milder clinical form. Seizures, hypotonia, lethargy, and hiccups are the principal symptoms, and many neonates/infants rapidly progress to coma. The diagnosis rests on clinical criteria, identification of high glycine levels in cerebrospinal fluid or in the breath, and genetic studies.
Nonketotic hyperglycinemia is a metabolic disorder of glycine, a neurotransmitter possessing both excitatory and inhibitory effects in the central nervous system (CNS)  . For this reason, the term glycine encephalopathy (GE) is often used in the literature to describe this condition    . The pathogenesis stems from mutations in genes that regulate the synthesis and activity of proteins involved in the glycine cleavage system (GCS), which is responsible for degradation of glycine    . But because of these mutations, abnormal concentrations of glycine accumulate in the CNS and the rest of the body, exerting severely toxic effects that arise soon after birth   . In up to 85% of cases with nonketotic hyperglycinemia, symptoms such as lethargy, myoclonic jerks, seizures, microcephaly hiccups, and generalized hypotonia appear in the early neonatal period    . Fatal outcomes in the first week of life are observed in up to 50% of cases . Those who survive through the neonatal manifestations of nonketotic hyperglycinemia suffer from serious retardation and failure to reach developmental milestones, whereas seizures, ataxia, and spastic diplegia are less frequently reported  . A somewhat delayed form of nonketotic hyperglycinemia is seen in about 20% of patients, in whom typical features do not start before 6 months of age, with a less severe symptomatology and minor developmental delay   . Some studies determined that the complaints may be aggravated by fever and a high protein diet .
The diagnosis of nonketotic hyperglycinemia is rarely made in practice, as incidence rates in isolated reports established its occurrence in approximately 1 in 55,000 individuals . Nevertheless, the physician must obtain a detailed history from the parents about the course and progression of signs, and perform a thorough physical examination that would confirm their presence. To make a diagnosis of nonketotic hyperglycinemia, specific tests that evaluate the concentrations of glycine in cerebrospinal fluid (CSF) should be performed  . The CSF/plasma ratio of glycine is highly suggestive of nonketotic hyperglycinemia  . In addition, the 13C-glycine breath test is regarded as a very useful exam for the identification of nonketotic hyperglycinemia, primarily because of its non-invasiveness  The ailment can be confirmed through enzyme assays and genetic testing that determine the exact mutations responsible for the disorder. Some authors recommend a biopsy of the liver as the optimal tissue for conducting these studies because the expression of these defects is not seen in fibroblast or lymphocytes   . A thorough family history might be an important tool in the assessment of patients, given the autosomal recessive pattern of inheritance.