[Hyperglycinemia without ketosis. Biochemical and enzymatic study]

Area of Science:

• Biochemistry
• Enzymology
• Neuroscience

Background:

• Non-ketotic hyperglycinemia (NKH) is a rare metabolic disorder.
• Elevated glycine levels in cerebrospinal fluid (CSF) and plasma are characteristic of NKH.
• The precise biochemical mechanisms and enzymatic defects in NKH require further elucidation.

Observation:

• Two neonatal cases of non-ketotic hyperglycinemia were studied.
• Glycine levels in plasma and CSF were monitored during a restrictive diet.
• Post-mortem analysis of liver and brain tissue was performed to assess glycine synthase activity.

Findings:

• High glycine concentrations in CSF and brain tissue were observed, correlating with neurological damage.
• A significant partial deficiency of glycine synthase activity was detected in the liver.
• A total deficiency of glycine synthase activity was found in the brain.
• Enzyme kinetics revealed normal glycine synthase affinity for glycine in patients, suggesting a reduced enzyme synthesis.

Implications:

• The findings suggest that reduced biosynthesis of the glycine synthase enzyme molecule is the primary cause of NKH.
• Understanding the enzymatic defect provides insights into the pathogenesis of brain damage in NKH.
• This study may inform future diagnostic and therapeutic strategies for non-ketotic hyperglycinemia.