Nonketotic Hyperglycinemia (NKH)

Description

• Disorder Characterized By:

  • Abnormally high levels of glycine (hyperglycinemia).
  • Accumulation primarily affects the brain leading to neurological issues.

• Forms:

  • Severe Form
  • Attenuated Form

• Onset:

  • Usually begins shortly after birth.
  • Attenuated form may begin later in infancy.

Severe Form

• Symptoms:

  • Extreme sleepiness leading to coma.
  • Weak muscle tone (hypotonia).
  • Life-threatening breathing issues.
  • Feeding difficulties, spasticity, profound intellectual disability.
  • Uncontrollable seizures.

• Developmental Milestones:

  • Most children do not achieve normal milestones like sitting up or grabbing objects.
  • Skill loss over time.

Attenuated Form

• Symptoms:
  • Similar to severe form but milder.
  • Delayed development but can achieve milestones.
  • Interactions possible often using sign language.
  • Possible mild, treatable seizures.
  • Other signs may include spasticity, involuntary movements (chorea), or hyperactivity.

Additional Features

• Brain Changes:

  • Visible in MRI.
  • Smaller corpus callosum in severe form.

• Prevalence:

  • Affects 1 in 76,000 worldwide.
  • Higher incidence in Finland and British Columbia.

Genetic Causes

• Gene Mutations:

  • GLDC and AMT genes.
  • GLDC mutations cause 80% of cases.
  • AMT mutations cause 20%.

• Glycine Cleavage System:

  • Enzymes break down excess glycine.
  • Disruption by mutations leads to glycine accumulation and reduced methyl group production.

• Activity Level:

  • Complete loss of enzyme activity leads to severe form.
  • Partial activity leads to attenuated form.

Inheritance Pattern

• Autosomal Recessive:
  • Mutations in both gene copies required.
  • Carrier parents usually asymptomatic.
  • Rarely due to de novo mutations.

Alternate Names

• Glycine encephalopathy
• NKH
• Non-ketotic hyperglycinemia

References

• Research articles and case studies available on PubMed for further reading.
• Key studies include works by Aliefendioglu et al., Applegarth & Toone, Coughlin et al., and Van Hove et al.