Classical homocystinuria

Alternative names Cystathionine β-synthase (CBS) deficiency
About the condition Classical homocystinuria is an amino acid disorder. It is a hereditary disease that is caused by a missing enzyme (cystathionine β-synthase) that is required to metabolise methionine and homocysteine. These are amino acids found in protein.
Inheritance Autosomal recessive
Year screening started in WA  2005
Incidence in Australia Approximately 1 in 100,000 births
Enzyme defect Disorder of the methionine trans-sulphuration pathway.
Symptoms if untreated
  • Mild to moderate intellectual disability
  • Seizures, psychiatric disturbances
  • Skeletal problems, including osteoporosis
  • Ocular problems, including dislocation of the lens of the eye
  • Thromboembolism
Metabolites on bloodspot screening
  • Increased methionine
  • Increased homocysteine (second-tier test)
Diagnostic tests
  • Plasma total homocysteine
  • Plasma amino acids
  • Urine amino and organic acids
  • CBS gene analysis
Treatment
  • Methionine-restricted diet with supplements
  • Betaine supplementation
  • Vitamin B6 may benefit some forms
  • Additional vitamin B12
Screening issues The vitamin B6-responsive form of CBS deficiency may be missed as methionine may not be increased in the first weeks of life.