Newborn screening for Fabry disease in Oregon: Approaching the iceberg of A143T and variants of uncertain significance

Sarah Viall, Anna Dennis, Amy Yang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Fabry disease newborn screening (NBS) has been ongoing in Oregon for over 41 months by first-tier enzyme quantitation and second-tier DNA testing. During that period the majority of abnormal referrals received (34/60) were for the presence of the controversial c.427G > A (p.Ala143Thr) aka A143T and the majority of non-A143T referrals were for other variants of uncertain significance (17/60) resulting in at least 32 infants with an inconclusive case outcome even after clinical evaluation and/or diagnostic testing. To date there has been no significant family history or onset of symptoms in individuals with an inconclusive outcome. Based on our experience, we have developed a framework for approaching A143T and other variants of uncertain clinical significance in an attempt to balance sensitivity with the unnecessary medicalization of healthy infants.

Original languageEnglish (US)
Pages (from-to)206-214
Number of pages9
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Volume190
Issue number2
DOIs
StatePublished - Jun 2022

Keywords

  • Fabry disease
  • lysosomal storage disorders
  • newborn screening

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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