National Center for Environmental Health

1. CDC Services Suzanne Cordovado, Ph.D. Team Lead, Molecular Quality Improvement Program Newborn Screening and Molecular Biology Branch, Division of Laboratory Sciences NCEH, CDC Tuesday, 28th June 2011 National Center for Environmental Health Centers for Disease Control and Prevention

2. Newborn Screening and Molecular Biology Branch Organization

3. The Newborn Screening Quality Assurance Program The only comprehensive quality assurance program using the dried-blood spots • Laboratory Services Provided by NSQAP • Filter paper evaluation • DBS reference and quality control materials • Proficiency Testing • Internet reporting site for laboratories • Follow-up of False negative results • Training, consultation, network resources

4. Translation Research Initiative Mission: Assure that the translation of research methods into routine laboratory tests for newborn screening leads to sustainable high-quality testing and healthier babies worldwide • Develop new screening methods for specific diseases • Integrate State Public Health Laboratories into the translation process through collaborative field studies • Expand global reach of newborn screening • Adapt innovative technologies for screening and quality assurance Ongoing collaboration between the CDC Foundation and NSMBB

5. Biochemical Mass Spectrometry Laboratory Mission Statement: Work with public health partners to develop new mass spectrometry-based assays to detect and monitor metabolic disorders, and enhance newborn screening laboratory performance through innovative approaches to biochemical marker detection. Selected Priorities: • Develop new methods for the analysis of dried-blood for metabolic screening and diagnosis of selected inborn errors of metabolism • Pilot program for MS/MS analyte ratios analysis for metabolic disorders to improve specificity of existing MS/MS-based newborn screening assays

6. Molecular Quality Improvement Program Mission: Work with public health laboratories to detect newborn disorders with molecular methods, and provide a public health forum to exchange molecular best practices, quality improvements and educational resources to enhance laboratory performance. • Molecular screening brings new and different technologies into the NBS laboratory creating a need for newborn screening laboratory resources • Second tier and primary molecular methods are now being used by a number of newborn screening laboratories

7. NBS Molecular Testing Status: 2010 36 state labs (denoted in green) offer a molecular test 84% of babies born/year

8. Molecular Quality Improvement Activities • Establishment of the NBS Molecular Network • Implementation of NBS Molecular Assessment Program (MAP) • QA research to identify and develop quality molecular methods for the DBS matrix • Molecular characterization of quality assurance (QA) materials (e.g. cystic fibrosis and hemoglobinopathies) • Translational research to address NBS community identified needs and QA protocols

9. Establishment of the NBS Molecular Network Public health partners working synergistically to enhance newborn screening with molecular tests • Facilitate a collaborative environment for knowledge and technology transfer between NBS labs • Assist labs in improving sensitivity and/or specificity of detection using primary or second-tier molecular tests • Collaborate with NBS labs to anticipate future molecular assays and needs 2010 NBS and Genetic Testing Symposium

10. NBS Molecular Network Goals Steering committee is comprised of NSMBB staff, Public Health partners and APHL • 1st meeting – February 23-24, 2011, Atlanta, GA • Goal 1: Prioritize disorders to implement molecular tests to enhance screening • Goal 2: Identify collaborative projects to fill gaps in molecular NBS • Goal 3: Plan strategies to enhance communication, education and dissemination of best molecular lab practices

11. Quality Assurance Research:Evaluation of DNA Extracted from DBS in NBS Assays • Determine DBS DNA extraction efficiency of commercially available extraction methods • Test downstream assay performance in NBS laboratories • Cystic fibrosis – InPlex CF (Hologic) and xTAGCF 39 (Luminex) • Galactosemia – in-house GALT assay • Hemoglobinopathies – in-house HBB assay • SCID – in-house TREC assay • State public health partners: California, Massachusetts, New York, Texas, Washington, and Wisconsin * *MQIP/NSMBB/CDC

12. Quality Assurance Research:CFTR Inplex Optimization for DNA from DBSCollaboration with Delaware NBS Laboratory • Determine minimum volume of input DNA from DBS for InPlex CF assay • DBS DNA is not routinely quantitated • Recommended input volume is 5 µl • Results indicate robust genotypes with input volumes > 2 µl • Samples tested: newborn DBS and NSQAP CFTR PT DBS • Analysis suggests probe sets 3905insT, 2184delA and W1282X fail more frequently when input DNA volume < 2 µl Low Probe Set Signals in Failed Samples

13. Future MQIP Projects • Web-based NBS molecular lab resource center • Guidelines/troubleshooting/education for molecular NBS assays • Discussion forum • Implementation of the Molecular Assessment Program • Provide quality management guidance and support for molecular testing in NBS laboratories • Partnership between MQIP, NBS laboratories and APHL • Research and Development to expand molecular testing • Population mutation panels • Creation of QA materials and services

14. Future MQIP Projects cont. • Characterization of hemoglobinopathies in PT samples – Ghanaian Collaboration • Confirm abnormal hemoglobin gene variants • Expanded CF Repository • Sustain and expand CF PT repository to include currently unavailable mutations • Create DBS QC materials for assay development and validation

15. Molecular Quality Improvement Program Team Members Suzanne Cordovado Team Lead SCordovado@cdc.gov Christopher Greene MAP Coordinator CGreene@cdc.gov Laura Hancock Web & Research Specialist LHancock@cdc.gov Miyono Hendrix Research Specialist MHendrix@cdc.gov Stanimila (Mimi) Nikolova Research Specialist SNikolova@cdc.gov Sean Mochal ORISE Fellow SMochal@cdc.gov Daniel Turner ORISE Fellow DTurner@cdc.gov National Center for Environmental Health Centers for Disease Control and Prevention