Nonketotic Hyperglycinemia: Two Case Reports and Review

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Nonketotic hyperglycinemia (NKH), also known as glycine encephalopathy, is an autosomal recessive metabolic disorder.
• It results from a defect in the glycine cleavage system, leading to excessive glycine accumulation, particularly in the central nervous system.
• NKH is a rare disorder with an estimated prevalence of 1:60,000, characterized by severe neonatal presentation.

Observation:

• Two neonates presented with neonatal encephalopathy, apnea, and progressive lethargy.
• Elevated cerebrospinal fluid (CSF) glycine levels and an increased CSF to plasma glycine ratio were indicative of classic NKH.
• Supportive findings included burst suppression electroencephalogram (EEG) patterns and agenesis of the corpus callosum.

Findings:

• The neonatal form of NKH presents with progressive encephalopathy, hypotonia, myoclonic jerks, seizures, and central apnea, often leading to death or severe developmental delay in survivors.
• Atypical forms exhibit heterogeneous and nonspecific disease courses, while classical glycine encephalopathy typically has a poor prognosis.
• Transient clinical stabilization and normalized plasma biochemistry may not accurately reflect the ongoing encephalopathic process.

Implications:

• Accurate diagnosis of NKH relies on biochemical evidence of glycine accumulation and characteristic EEG findings.
• Serial EEGs are essential for monitoring disease progression and evaluating the efficacy of therapeutic interventions.
• Understanding the nuances of NKH presentation and disease course is critical for optimizing patient management and prognosis.