newborn screening

by Laura Russell , MPH , specialist , Newborn Screening and Genetics

The Value of Gene Sequencing in Newborn Screening

For some disorders , such as Phenylketonuria ( PKU ) and Medium-Chain Acyl-coA Dehydrogenase Deficiency ( MCAD ) the biochemical test is sufficient , and knowing the genotype does not change the treatment outcome . So one main issue that was discussed extensively during the meeting was how NBS programs can determine if sequencing adds value to a particular test . Participants identified a need for guidance on which disorders should be considered for gene sequencing , as well as resources involved , legal and ethical considerations , determination of benefit to the baby and reduction in health disparities . In response , the NBS Molecular Subcommittee is developing an implementation decision matrix , which will include considerations in determining whether to perform sequencing in-house or utilize a regional laboratory .

Participants also outlined key laboratory and follow-up barriers to incorporating gene sequencing into their screening algorithms . For laboratory staff , a need exists for hands-on training in the instrumentation and methods involved . The New York Department of Health NBS Program was one of three state NBS programs recently awarded funding through the APHL Newborn Screening Technical Assistance and Evaluation Program ( NewSTEPs ) as a peer network resource center for NBS . The program plans to allocate a portion of this funding to pilot a sequencing workshop tailored to specific program needs , which will inform implementation of peer network training within other NBS programs .

Follow-up staff identified a need for resources to address knowledge barriers , as they reported a lack of public health genetic expertise and difficulty in communicating test results to clinicians . To address this barrier , the Subcommittee will collaborate with the NewSTEPs Short Term Follow-Up Workgroup to develop online educational resources .

Tracking Variants of Unknown Significance

Tracking variants of unknown significance ( VUS ) was identified as a key barrier by both laboratory and follow-up staff . Currently there is no central database of genetic variants for the many NBS conditions that may involve sequencing and a lack of guidance on updating families when new information becomes available . To address these issues , the Subcommittee is developing an NBS-specific mutation database , and plans to collaborate with the Newborn Screening Translational Research Network to create guidance documents on tracking children with VUS .

Participating NBS programs indicated that they plan to incorporate gene sequencing primarily as a second-tier test as part of their testing algorithms . In an effort to monitor progress and provide further technical assistance , the Subcommittee will hold an evening follow-up session at the APHL Newborn Screening and Genetic Testing Symposium to be held September 10-13 , 2017 , in New Orleans , LA . The Subcommittee will continue to monitor trends in the utility of gene sequencing in public health NBS and offer guidance where appropriate .

Attendees from the Gene Sequencing in Public Health NBS Meeting , held in collaboration with the US Centers for Disease Control and Prevention and the Health Resources and Services Administration , represented about 40 NBS programs and federal stakeholders .