Additional Notes

Nonketotic Hyperglycinemia (NKH, also known as glycine encephalopathy) is a rare inborn error of glycine metabolism characterized by a deficiency in the glycine cleavage enzyme system leading to accumulation of glycine throughout the body, especially in the central nervous system. The disorder is diagnosed biochemically by elevated glycine levels in the cerebrospinal fluid (CSF) and plasma with an increased CSF: plasma glycine ratio. Phenotypically, individuals with this disorder present in the neonatal or infantile period, up to 3 months of age, with lethargy, hypotonia, seizures, and apnea, leading to early death or various degrees of intellectual disability and intractable seizures. A small subset of individuals may also present with milder symptoms after 3 months of age. Based on outcomes, NKH can be severe or attenuated. Onset in the neonatal or infantile period usually results in severe NKH with no developmental progress and intractable epilepsy. Individuals with onset later than 3 months of age and about half of those with infantile onset, exhibit attenuated NKH with variable developmental progress, and treatable or no epilepsy.