A revisit to the natural history of homocystinuria due to cystathionine beta-synthase deficiency

Mol Genet Metab. 2010 Jan;99(1):1-3. doi: 10.1016/j.ymgme.2009.09.009.


We review the evidence that in Denmark and probably certain other European countries the number of individuals identified with homocystinuria due to homozygosity for the widespread c.833T>C (p.I278T) mutation in the gene that encodes cystathionine beta-synthase (CBS) falls far short of the number of such individuals expected on the basis of the heterozygote frequency for this mutation found by molecular screening. We conclude that the predominant portion of such homozygotes may be clinically unaffected, or may be ascertained for thromboembolic events occurring no sooner than the third decade of life. If so, there was significant ascertainment bias in the time-to-event curves previously published describing the natural history of untreated CBS deficiency Mudd et al. and these curves should be used with care.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Cystathionine beta-Synthase / deficiency
  • Cystathionine beta-Synthase / genetics*
  • Denmark / epidemiology
  • Gene Frequency
  • Genotype
  • Homocystinuria / enzymology
  • Homocystinuria / epidemiology
  • Homocystinuria / genetics*
  • Humans
  • Incidence
  • Infant, Newborn
  • Mutation, Missense*
  • Neonatal Screening


  • Cystathionine beta-Synthase