Lecture Notes

Glycine disorders, also known as glycine encephalopathy or nonketotic hyperglycinemia (NKH), are a group of rare neurometabolic disorders where glycine, an amino acid, accumulates in the body, particularly in the brain, due to a defect in glycine metabolism

• Primary Glycine Disorder: Nonketotic hyperglycinemia (NKH), also known as glycine encephalopathy
  • Caused by deficiency of the glycine cleavage enzyme
  • Leads to accumulation of glycine in the body
  • All forms result in cerebral dysfunction
• Function of the Glycine Cleavage Enzyme:
  • Breaks glycine into carbon dioxide and ammonia
  • Transfers a methyl group to tetrahydrofolate → forms methylenetetrahydrofolate
  • Consists of four subunits:
    • P-protein: Pyridoxal-phosphate dependent
    • H-protein: Hydrogen carrier, requires lipoylation
    • T-protein: Requires tetrahydrofolate
    • L-protein: Lipoamide dehydrogenase
• Secondary Enzyme Deficiencies:
  • Disorders affecting pyridoxal-phosphate (e.g., PNPO deficiency) can cause secondary NKH
  • Disorders in protein lipoylation result in variant forms of NKH
• Neonatal Presentation of NKH:
  • Typically occurs in the first week of life
  • Symptoms include:
    • Lethargy and poor feeding
    • Progression to coma
    • Frequent hiccupping and seizures
    • Severe hypotonia
    • Characteristic burst suppression pattern on EEG
  • Spontaneous recovery of respiratory function typically occurs within 3 weeks
• Infantile Presentation of NKH:
  • Symptoms include:
    • Hypotonia
    • Lethargy
    • Seizures (spasms or myoclonic)
  • EEG findings:
    • Multifocal epilepsy
    • Hypsarrhythmia