Lab Matters Summer 2018 | Page 81

APHL 2018 Annual Meeting Poster Abstracts

Newborn Screening

Playing with Building Blocks : The Newborn Screening Health IT Implementation Guide and Toolkit

M . K . Yost-Daljev 1 , S . Downer 1 , A . Padgett 1 , J . Miller 2 , W . Andrews 3 ; 1 J Michael Consulting , Atlanta , GA , 2 Colorado School of Public Health , Denver , CO , 3 Virginia Division of Consolidated Laboratory Services , Richmond , VA

Background : Health information technology ( HIT ) continues to play a crucial role in improving newborn screening ( NBS ) processes . A key component of HIT is utilizing Health Level 7 ( HL7 ) to send laboratory orders and test results between providers and the NBS laboratory . Several NBS programs have implemented , or are in the process of implementing , HL7 messaging using program-specific methodologies with varying levels of success . This disparate nature of implementation has produced inconsistent results and served as the impetus for the development of a NBS HIT resource guide and toolkit to provide guidance for programs implementing electronic messaging . Objective : To introduce the NBS HIT Resource Guide and Toolkit to the NBS community , educate them on the value of the guide and facilitate an interactive discussion of it . Next steps for expanding the guide to other areas of HIT beyond electronic messaging will also be discussed .

Methods : The NewSTEPs 360 project , funded by the Health Resources and Services Administration ( HRSA ), works with NBS programs to improve timeliness of NBS from birth to results reporting . This includes activities to implement HIT solutions including electronic messaging . NewSTEPs 360 partnered with the Virginia Division of Consolidated Laboratory Services ( DCLS ) and J Michael Consulting ( JMC ) to bring together NBS programs , at various stages of electronic messaging implementation and several national partners to author a NBS HIT Resource Guide and Toolkit .

Results : Representatives met for an in-person meeting in February 2017 , which resulted in a detailed outline of NBS electronic messaging processes based on their diverse experiences . This outline will be developed into a resource guide planned for release by the end of August 2017 . This first version will lead a NBS program through the steps needed to plan , implement and maintain an electronic messaging project including details on such activities as establishing partnerships , workflow mapping and message validation among others . The modular nature of the guide will allow the reader to utilize the sections that are important for their project status while setting aside the sections that are not relevant . The guide will also provide descriptions of the tasks needed to meet milestones , tools for accomplishing those tasks and case studies from programs that have completed milestones highlighting lessons learned .

Conclusion : This poster will introduce participants to the NBS HIT Resource Guide and Toolkit , walk them through the layout and explain its utility .

Presenter : Willie Andrews , Virginia Division of Consolidated Laboratory Services , Richmond , VA , Phone 804.648.4480 , Email : willie . andrews @ dgs . virginia . gov

Validation of a Six-Gene Next Generation Sequencing ( NGS ) Panel for Second-Tier Newborn Screening

H . Schwab , R . Sicko , C . Stevens , D . Kay , C . Saavedra-Matiz and M . Caggana , Wadsworth Center , New York State Department of Health , Albany , NY

Background : The New York State ( NYS ) newborn screening ( NBS ) program has developed a six-gene next generation sequencing ( NGS ) panel to replace Sanger sequencing as a second-tier test for Pompe disease , Krabbe disease , mucopolysaccharidosis type I ( MPS-I ), X-linked adrenoleukodystrophy ( X-ALD ), very long-chain acyl- CoA dehydrogenase deficiency ( VLCADD ) and medium-chain acyl- CoA dehydrogenase deficiency ( MCADD ). These inherited metabolic disorders often result in death in infancy or childhood . With timely diagnosis , treatment may improve morbidity and / or mortality . In NYS , the current testing algorithm involves first-tier tandem mass spectrometry followed by second-tier Sanger sequencing . Sanger assays are expensive , labor intensive and cannot detect large , heterozygous deletions and duplications ( del / dup ). Since these conditions are autosomal recessive ( except for X-ALD ), all infants with a single mutation must be referred for diagnostic testing and clinical evaluation , as they may carry an undetected del / dup . Many infants who are carriers and will never develop disease are referred , leading to unnecessary follow-up testing and undue emotional stress for families . In 2016 , 125 infants were referred for confirmatory testing for these six conditions , though only 21 infants were confirmed to have disease .

Objective : The aim of this project is to validate the six-gene panel and to replace the individual Sanger sequencing assays that are currently in place for these six conditions . The validation will include testing to assess the analytical and clinical validity of the panel , including accuracy and reproducibility testing . Turnaround time and cost will also be assessed .

Methods : A TruSeq Custom Amplicon ( TSCA ) panel , which uses 178 amplicons to target regions of the GAA , IDUA , GALC , ABCD1 , ACADVL and ACADM genes was designed . DNA from a well-characterized genomic DNA ( Coriell cell line NA12878 ) and 30 dried blood spot ( DBS ) samples previously screened by the NYS program will be run on the panel . DNA will be extracted from a single 3-mm punch DBS per sample and 10 ng will be used to prepare sequencing libraries , which will be run on an Illumina MiSeq using a version 2 flow cell with 300 cycles . A bioinformatics pipeline will be developed and variant calling and analysis will allow for the identification of genetic variants , including the detection of del / dups with copy number algorithms . The panel will be assessed by comparison to Sanger results and evaluation of the Coriell DNA .

Conclusions : Implementation of this panel may improve the current algorithms used in NYS by decreasing false positive referral rates , if only infants with two mutations can be referred . It will also be possible to expand the panel to include additional conditions , allowing for additional cost-savings .

Presenter : Holly Schwab , Wadsworth Center , New York State Department of Health , Albany , NY , Phone : 518.705.0417 , Email : schwabh4444 @ gmail . com

Newborn Screening