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.