Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening

Derek Wong, Silvia Tortorelli, Lisa Bishop, Elizabeth A. Sellars, Lisa A. Schimmenti, Natalie Gallant, Carlos E. Prada, Robert J. Hopkin, Nancy D. Leslie, Susan A. Berry, David S. Rosenblatt, Amy L. Fair, Dietrich Matern, Kimiyo Raymond, Devin Oglesbee, Piero Rinaldo, Dimitar Gavrilov

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Purpose:We evaluated the clinical outcome in homocysteine remethylation disorders following newborn screening (NBS) and initiation of early specific treatment.Methods:Five patients with remethylation disorders were included in this study.Results:Two asymptomatic patients (one with cblG and one with cblE) were identified by NBS using an approach that combines a postanalytical interpretive tool (available on the Region 4 Stork (R4S) collaborative project website, http://www.clir-r4s.org) and a second-tier test for total homocysteine determination. Both the initial screening and the second-tier test are performed on the same blood spot, with no additional patient contact, resulting in no false-positive outcomes. Two additional patients with methylenetetrahydrofolate reductase deficiency were detected by NBS using low methionine as a marker. Although already symptomatic despite the early diagnosis, the latter two patients greatly improved with treatment and their outcomes are compared with that of another patient with methylenetetrahydrofolate reductase deficiency and significant morbidity who was diagnosed clinically at 3 months of age.Conclusion:Early detection by NBS and timely and specific treatment considerably improve at least short-term outcomes of homocysteine remethylation disorders. When a remethylation disorder is suspected, group-specific treatment could be started prior to the completion of in vitro confirmatory testing because all disorders from this group require similar intervention.

Original languageEnglish (US)
Pages (from-to)162-167
Number of pages6
JournalGenetics in Medicine
Issue number2
StatePublished - Feb 1 2016


  • Region 4 Stork tool
  • Remethylation disorders
  • homocysteine
  • newborn screening
  • second-tier testing

ASJC Scopus subject areas

  • Genetics(clinical)


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