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Newborn Screening Molecular Assessment Program for quality improvement
136
Abstracts
b
The Hospital for Sick Children, Division of Respiratory Medicine, Toronto, Ontario, Canada c The Hospital for Sick Children, Division of Gastroenterology, Hepatology, and Nutrition, Toronto, Ontario, Canada Newborn screening (NBS) for cystic fibrosis (CF) in Ontario involves immunoreactive trypsinogen (IRT) measurement followed by the analysis of the CFTR gene using a common mutation panel as second tier testing. Category C screen positive cases represent infants where the IRT level is N99.9th percentile and no common mutations are detected. Since April 2008, our center has received 305 Category C screen positive referrals. Three of these infants were subsequently confirmed to have CF. The IRT levels on the NBS of these three babies were 341 ng/mL, 232 ng/mL, and 202 ng/mL. Two babies were premature (gestational age of b37 weeks), and one was delivered at 37 weeks. An admission to the nursery was required for two of the three neonates. At the time of retrieval for diagnostic evaluation, all three infants were either struggling with weight gain or had feeding issues. The initial sweat chloride test in one infant was abnormal (N60 mmol/L), and borderline (30–60 mmol/L) in two infants. One of the two children with a borderline sweat test was subsequently admitted for pertussis and the other for a low hemoglobin level requiring transfusion, low albumin, and breathing difficulties. All three infants were identified to be pancreatic insufficient. Two of the three families are consanguineous and sequencing of the CFTR gene identified disease-causing mutations in all cases. This series of case examples illustrates that despite the high false positive rate in Category C screening, individual patients with significant, early disease manifestations would be missed if such screening was to be abandoned.
doi:10.1016/j.clinbiochem.2014.07.034
Describing the utility of the newborn screening Molecular Assessment Program (MAP) in US Public Health Laboratories Ruhiyyih A. Degeberg a, Jelili Ojodu a, Christopher R. Greene b, Suzanne N. Cordovado b, Carla D. Cuthbert b a Association of Public Health Laboratories, Silver Spring, MD, USA b Newborn Screening Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Objectives: To measure the utility of the newborn screening Molecular Assessment Program (MAP) site visit through the use of a post-visit evaluation tool. MAP is a non-regulatory, voluntary, peer evaluation site visit program, which began in 2011. The purpose of MAP was to bring together state and federal experts in newborn screening molecular testing to evaluate public health laboratory programs and offer suggestions for quality improvements to their ongoing molecular assays as well as provide guidance for implementing future molecular assays. Methods: MAP has performed site visits for 10 state newborn screening laboratories. To evaluate the utility of this program and the resulting summary report, a questionnaire was sent to each laboratory after they received the requested visit and follow-up summary report. Evaluation criteria were designed to establish why the program had requested the visit, what the visit accomplished, what the report accomplished, and what effects may have been seen in overall molecular testing in subsequent regulatory inspections. Results: The most common changes reported following the visit included: revisions in standard operating procedures and altering laboratory space and workflow to better accommodate the unique molecular testing requirements. Additionally, after the MAP site visit, 67% of labs reported either no molecular testing deficiencies or fewer
molecular deficiencies cited in laboratory regulatory inspections once the MAP recommended quality improvement suggestions were implemented. Conclusions: MAP has been shown to be successful in addressing molecular testing quality improvement for US newborn screening laboratories.
doi:10.1016/j.clinbiochem.2014.07.035
Newborn Screening Molecular Assessment Program for quality improvement Christopher N. Greene, Carla D. Cuthbert, Suzanne K. Cordovado Newborn Screening Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Objectives: To create and implement a molecular assessment site visit and consultation program specific for newborn screening (NBS) molecular testing. The introduction of molecular tests from dried blood spots (DBS) for second-tier cystic fibrosis genotyping and primary SCID screening has been disruptive due to lack of molecular screening-specific quality assurance guidance. The Molecular Assessment Program (MAP), developed by the U.S. Centers for Disease Control and Prevention in partnership with the Association of Public Health Laboratories, helps NBS laboratories improve the quality of laboratory practices and test performance through an invited site review from state and federal molecular biologists. Methods: Evaluation criteria were modeled from multiple national and state regulatory requirements and published good laboratory practices and guidelines for molecular testing. MAP guidance covers multiple laboratory processes including laboratory documentation, workflow, assay validation and results reporting. Feedback is provided in an exit discussion and a confidential written report to the program. Results: After performing ten site visits, several common challenges were identified for NBS molecular assays including modifying workspace for unidirectional workflow, assay validation guidelines, defining molecular-specific quality assurance processes and harmonization of standard operating procedures. Some of the outcomes from the MAP visits include inter-program collaborations for quality control materials and processes, laboratory expansion and reorganization to accommodate molecular workflow, molecular specific staff development recommendations, and valuable feedback to CDC for DBS quality control development and training needs. Conclusions: The MAP site visits facilitate implementation of best molecular practices and are a useful tool for continual NBS program quality improvement.
doi:10.1016/j.clinbiochem.2014.07.036
Continuous gene deletion syndrome in two families involving OTC, RPGR and TSPAN7 genes, presenting as ornithine transcarbamylase deficiency Shailly Jain-Ghai a, Stephanie Skinner a, Jessica Hartley b, Cheryl Greenberg b, Alicia Chan a a Stollery Children's Hospital, Edmonton, Alberta, Canada b University of Manitoba, Winnipeg, Manitoba, Canada Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. The classic presentation in males is hyperammonemic encephalopathy in the early neonatal period. Given its
Abstracts
b
The Hospital for Sick Children, Division of Respiratory Medicine, Toronto, Ontario, Canada c The Hospital for Sick Children, Division of Gastroenterology, Hepatology, and Nutrition, Toronto, Ontario, Canada Newborn screening (NBS) for cystic fibrosis (CF) in Ontario involves immunoreactive trypsinogen (IRT) measurement followed by the analysis of the CFTR gene using a common mutation panel as second tier testing. Category C screen positive cases represent infants where the IRT level is N99.9th percentile and no common mutations are detected. Since April 2008, our center has received 305 Category C screen positive referrals. Three of these infants were subsequently confirmed to have CF. The IRT levels on the NBS of these three babies were 341 ng/mL, 232 ng/mL, and 202 ng/mL. Two babies were premature (gestational age of b37 weeks), and one was delivered at 37 weeks. An admission to the nursery was required for two of the three neonates. At the time of retrieval for diagnostic evaluation, all three infants were either struggling with weight gain or had feeding issues. The initial sweat chloride test in one infant was abnormal (N60 mmol/L), and borderline (30–60 mmol/L) in two infants. One of the two children with a borderline sweat test was subsequently admitted for pertussis and the other for a low hemoglobin level requiring transfusion, low albumin, and breathing difficulties. All three infants were identified to be pancreatic insufficient. Two of the three families are consanguineous and sequencing of the CFTR gene identified disease-causing mutations in all cases. This series of case examples illustrates that despite the high false positive rate in Category C screening, individual patients with significant, early disease manifestations would be missed if such screening was to be abandoned.
doi:10.1016/j.clinbiochem.2014.07.034
Describing the utility of the newborn screening Molecular Assessment Program (MAP) in US Public Health Laboratories Ruhiyyih A. Degeberg a, Jelili Ojodu a, Christopher R. Greene b, Suzanne N. Cordovado b, Carla D. Cuthbert b a Association of Public Health Laboratories, Silver Spring, MD, USA b Newborn Screening Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Objectives: To measure the utility of the newborn screening Molecular Assessment Program (MAP) site visit through the use of a post-visit evaluation tool. MAP is a non-regulatory, voluntary, peer evaluation site visit program, which began in 2011. The purpose of MAP was to bring together state and federal experts in newborn screening molecular testing to evaluate public health laboratory programs and offer suggestions for quality improvements to their ongoing molecular assays as well as provide guidance for implementing future molecular assays. Methods: MAP has performed site visits for 10 state newborn screening laboratories. To evaluate the utility of this program and the resulting summary report, a questionnaire was sent to each laboratory after they received the requested visit and follow-up summary report. Evaluation criteria were designed to establish why the program had requested the visit, what the visit accomplished, what the report accomplished, and what effects may have been seen in overall molecular testing in subsequent regulatory inspections. Results: The most common changes reported following the visit included: revisions in standard operating procedures and altering laboratory space and workflow to better accommodate the unique molecular testing requirements. Additionally, after the MAP site visit, 67% of labs reported either no molecular testing deficiencies or fewer
molecular deficiencies cited in laboratory regulatory inspections once the MAP recommended quality improvement suggestions were implemented. Conclusions: MAP has been shown to be successful in addressing molecular testing quality improvement for US newborn screening laboratories.
doi:10.1016/j.clinbiochem.2014.07.035
Newborn Screening Molecular Assessment Program for quality improvement Christopher N. Greene, Carla D. Cuthbert, Suzanne K. Cordovado Newborn Screening Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Objectives: To create and implement a molecular assessment site visit and consultation program specific for newborn screening (NBS) molecular testing. The introduction of molecular tests from dried blood spots (DBS) for second-tier cystic fibrosis genotyping and primary SCID screening has been disruptive due to lack of molecular screening-specific quality assurance guidance. The Molecular Assessment Program (MAP), developed by the U.S. Centers for Disease Control and Prevention in partnership with the Association of Public Health Laboratories, helps NBS laboratories improve the quality of laboratory practices and test performance through an invited site review from state and federal molecular biologists. Methods: Evaluation criteria were modeled from multiple national and state regulatory requirements and published good laboratory practices and guidelines for molecular testing. MAP guidance covers multiple laboratory processes including laboratory documentation, workflow, assay validation and results reporting. Feedback is provided in an exit discussion and a confidential written report to the program. Results: After performing ten site visits, several common challenges were identified for NBS molecular assays including modifying workspace for unidirectional workflow, assay validation guidelines, defining molecular-specific quality assurance processes and harmonization of standard operating procedures. Some of the outcomes from the MAP visits include inter-program collaborations for quality control materials and processes, laboratory expansion and reorganization to accommodate molecular workflow, molecular specific staff development recommendations, and valuable feedback to CDC for DBS quality control development and training needs. Conclusions: The MAP site visits facilitate implementation of best molecular practices and are a useful tool for continual NBS program quality improvement.
doi:10.1016/j.clinbiochem.2014.07.036
Continuous gene deletion syndrome in two families involving OTC, RPGR and TSPAN7 genes, presenting as ornithine transcarbamylase deficiency Shailly Jain-Ghai a, Stephanie Skinner a, Jessica Hartley b, Cheryl Greenberg b, Alicia Chan a a Stollery Children's Hospital, Edmonton, Alberta, Canada b University of Manitoba, Winnipeg, Manitoba, Canada Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. The classic presentation in males is hyperammonemic encephalopathy in the early neonatal period. Given its