A single NGS‐based assay covering the entire genomic sequence of the DMD gene facilitates diagnostic and newborn screening confirmatory testing

2021 ◽  
Vol 42 (5) ◽  
pp. 626-638
Author(s):  
Babi R. R. Nallamilli ◽  
Alka Chaubey ◽  
C. A. Valencia ◽  
Leah Stansberry ◽  
Andrea M. Behlmann ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Genomic Sequence ◽  
Confirmatory Testing ◽  
Dmd Gene ◽  
Entire Genomic Sequence

scholarly journals Successful Implementation of Newborn Screening for Hemoglobin Disorders in the Philippines

2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Carmencita D. Padilla ◽  
Bradford L. Therrell ◽  
Maria Melanie Liberty B. Alcausin ◽  
Reynaldo C. de Castro ◽  
Maria Beatriz P. Gepte ◽  
...  
Keyword(s):  
Newborn Screening ◽  
High Performance ◽  
Population Data ◽  
The Philippines ◽  
Successful Implementation ◽  
Clinical Experiences ◽  
Term Care ◽  
Confirmatory Testing ◽  
Newborn Bloodspot Screening

The Philippine newborn bloodspot screening (NBS) program began in 1996 with 24 hospitals and was formalized by legislation in 2004. The NBS panel was recently expanded to include a number of additional hereditary congenital conditions. Expertise and experiences from other NBS programs already screening for hemoglobinopathies were essential to its successful integration into the ongoing dried bloodspot NBS program in the Philippines. Building on clinical experiences and population data from Filipinos born in California, USA, hemoglobinopathies (including thalassemias) were selected for inclusion in the expanded screening panel. Hemoglobinopathy NBS, using high performance liquid chromatography, was implemented in a stepwise manner into the seven regional NBS screening laboratories. A central university laboratory provides confirmatory testing using both capillary electrophoresis and molecular methodologies. NBS results indicating carriers are followed up with educational fact sheets, while results of presumptive disease are referred for confirmatory testing and follow-up with a hematologist. Long-term care is provided through newborn screening continuity clinics across the country. Hemoglobinopathy NBS is now included in the national insurance package and screening uptake continues to increase nationally, exceeding 90% of all newborns in 7400+ hospitals and birthing centers nationwide prior to the COVID-19 pandemic.

scholarly journals National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Follow-Up Testing for Metabolic Disease Identified by Expanded Newborn Screening Using Tandem Mass Spectrometry; Executive Summary

2009 ◽  
Vol 55 (9) ◽  
pp. 1615-1626 ◽  
Author(s):  
Dennis J Dietzen ◽  
Piero Rinaldo ◽  
Ronald J Whitley ◽  
William J Rhead ◽  
W Harry Hannon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Tandem Mass Spectrometry ◽  
Organic Acids ◽  
Newborn Screening ◽  
Tandem Mass ◽  
Confirmatory Testing ◽  
The Us ◽  
The Impact

Abstract Background: Almost all newborns in the US are screened at birth for multiple inborn errors of metabolism using tandem mass spectrometry. Screening tests are designed to be sufficiently sensitive so that cases are not missed. The NACB recognized a need for standard guidelines for laboratory confirmation of a positive newborn screen such that all babies would benefit from equal and optimal follow-up by confirmatory testing. Methods: A committee was formed to review available data pertaining to confirmatory testing. The committee evaluated previously published guidelines, published methodological and clinical studies, clinical case reports, and expert opinion to support optimal confirmatory testing. Grading was based on guidelines adopted from criteria derived from the US Preventive Services Task Force and on the strength of recommendations and the quality of the evidence. Three primary methods of analyte measurement were evaluated for confirmatory testing including measurement of amino acids, organic acids, and carnitine esters. The committee graded the evidence for diagnostic utility of each test for the screened conditions. Results: Ample data and experience were available to make strong recommendations for the practice of analyzing amino acids, organic acids, and acylcarnitines. Likewise, strong recommendations were made for the follow-up test menu for many disorders, particularly those with highest prevalence. Fewer data exist to determine the impact of newborn screening on patient outcomes in all but a few disorders. The guidelines also provide an assessment of developing technology that will fuel a refinement of current practice and ultimate expansion of the diseases detectable by tandem mass spectrometry. Conclusions: Guidelines are provided for optimal follow-up testing for positive newborn screens using tandem mass spectrometry. The committee regards these tests as reliable and currently optimal for follow-up testing. .

scholarly journals Implementing a tracking system for confirmatory diagnostic results after positive newborn screening for cystic fibrosis—implications for process quality and patient care

2020 ◽  
Author(s):  
Gwendolyn Gramer ◽  
Inken Brockow ◽  
Christiane Labitzke ◽  
Junmin Fang-Hoffmann ◽  
Andreas Beivers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Patient Care ◽  
Tracking System ◽  
Process Quality ◽  
Federal State ◽  
Cost Calculation ◽  
Confirmatory Testing ◽  
Before And After

Abstract Newborn screening for cystic fibrosis (CF-NBS) was introduced in Germany in 2016. Currently, systematic follow-up of positive CF-NBS results is not implemented or reimbursed in the NBS program. We investigated results of confirmatory testing over 24 months after implementation of CF-NBS for a large German NBS center before and after introduction of an active tracking system and performed a cost calculation for tracking. Results are compared with the federal state of Bavaria, where a centralized tracking system has been in place for many years. At the NBS center, 244 of 281,907 children had a positive CF-NBS result requiring diagnostic confirmation. Before implementation of a telephone tracking system, only 43% of confirmatory results were returned despite repeated written requests. The consecutive strategy including telephone tracking led to an increase of resolved cases to 84%. However, the centralized tracking system in Bavaria, assigning children with positive CF-NBS directly to a responsible CF-center, resolved 99% of cases. The calculated additional cost for a tracking system in Germany including telephone tracking is 1.20€ per newborn screened. Conclusion: The implementation of a tracking system achieves a distinct improvement in CF-NBS with justifiable costs. The effect can be limited by absence of centralized organization of confirmatory testing. What is Known:• Newborn screening for cystic fibrosis (CF-NBS) has been performed for many years in several countries worldwide• While many studies have focused on different CF-NBS strategies, the organization of confirmatory testing and process quality concerning returned information to the NBS center has so far received less attention. What is New:• The implementation of an active tracking system achieves a distinct improvement of clarified cases after positive CF-NBS with justifiable costs.• The effect of a tracking system can be limited by the absence of a centralized organization of confirmatory testing.

scholarly journals Role of Point-of-Care Device in Improving Sickle Cell Newborn Screening Feasibility in Haiti

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3670-3670
Author(s):  
Ofelia A. Alvarez ◽  
Tally Hustace ◽  
Mimose Voltaire ◽  
Rodrigueson Rizil ◽  
Ulrick Liberus ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Point Of Care ◽  
Screening Method ◽  
Beta Thalassemia ◽  
Blood Samples ◽  
Confirmatory Testing ◽  
Hemoglobin C

Abstract Introduction: Until 2017, hemoglobinopathy newborn screening (NBS) was not offered in Haiti, a country with about 243,000 births per year. Sickle SCAN is a rapid point-of-care (POC) with lateral flow immunoassay technology, but its role in NBS is unknown. Recently, over 100 dried blood samples from newborns were tested [Nguyen-Khoa T, Ann Biol Clin (Paris), 2018] in France with accurate results. Objective: This work had the objective to be proof-of-concept that a hospital-based NBS program is feasible in Haiti and to examine the role of Sickle SCAN in NBS in a larger sample size. Methods: The Ethics Committee at the Universitaire Justinien Hospital (HUJ) and the Institutional Review Board at the University of Miami approved this study. We formed a Haitian team composed of a pediatrician on staff (RSF), two dedicated NBS nurses, a program coordinator (MV), two community health workers, a laboratory technician (RR), and a data manager (UL). We acquired isoelectric focusing equipment (IEF) and performed NBS from dried blood samples only for the first three months while the technician gained proficiency. Thereafter, we have performed dual screening method with the POC device Sickle SCAN and IEF. Confirmatory testing was obtained with both methods. Data were entered into RED Cap. Results: Beginning in August 2017 until present (June 2018), we have screened 1,800 newborns, of which 10.5% have sickle cell trait, 3.3% have hemoglobin C trait, 0.78% have hemoglobin SS, 0.27% have hemoglobin SC and one child has been confirmed to have sickle beta thalassemia plus. Currently, there are 15 children followed at HUJ, for a SCD incidence of 0.83% (8 SS, 6 SC and 1 S-beta thalassemia+). Before the POC screening was implemented two infants have already died when the mothers were contacted (one who screened positive for FS and another for FC). The POC allows for immediate referral and penicillin prophylaxis for at-risk children until the cases are confirmed. Systemic barriers encountered are the electrical outages and intense heat which impacted IEF performance, material procurement (laboratory materials, NBS materials, oral penicillin) which are dependent of shipments from outside of Haiti. Conclusions: A hospital-based NBS Program is feasible. SCD is highly prevalent with an incidence of 0.83% among newborns in the population studied. Based on this incidence, we estimate that every year around 2,000 children will be born with sickle cell disease in Haiti. The point-of-care device enhanced the screening program by obtaining immediate screening results and maximizing family notification for confirmatory testing. Disclosures No relevant conflicts of interest to declare.

Evaluation of a Novel Newborn Screening Follow-up Program for Infants with Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2344-2344
Author(s):  
Emily Riehm Meier ◽  
Kisha Hampton ◽  
Ellen Bloom ◽  
Natalie Duncan ◽  
Chris Roberson ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Sickle Cell Disease ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Home Visit ◽  
Dna Testing ◽  
Cell Disease ◽  
Confirmatory Testing ◽  
The Mean

Abstract While newborn screening for sickle cell disease (SCD) has improved survival of affected infants through early prescription of prophylactic penicillin and SCD education for the parents, newborn screening follow-up programs are highly variable among states. The novel statewide newborn screening program in Indiana, Sickle SAFE (Screening, Assessment, Follow-up, Education), was started in 2009 and followed infants through the first year of life until 2013 when the program expanded to provide follow-up for the first 5 years of life. Sickle SAFE ensures timely notification and education of families of affected patients and links them to a hematologist. An initial home visit is scheduled and coordinated by the Sickle SAFE Program Coordinator within one month of receipt of abnormal screening results. After the initial home visit, coordinators maintain phone contact with families regularly throughout the enrollment period. An analysis of Georgia Medicaid claims published in 2016 reported that 47.2% of children between 2 and 3 years of age had screening transcranial Doppler (TCD) and 73.6% received PPSV23 (Pneumovax). The current study aims to assess the rates of attainment for recently published quality indicators of pediatric SCD care for children enrolled in Sickle SAFE. A retrospective study was initiated to determine the proportion of children enrolled in Sickle SAFE who received TCD screening between 2 and 3 years of age (HbFS only) and influenza and pneumococcus [PCV (Prevnar) and PPSV23] vaccination. The mean age at confirmatory testing and receipt of penicillin prophylaxis (goal ≤ 2 months) as well as the mean age of the affected infant when families were offered genetic counseling (goal ≤ 6 months) were calculated. From 2009-2012, all positive newborn screens for any sickle hemoglobinopathy were reflexively sent for confirmatory DNA testing. From 2013 onward, only HbFS newborn screens were sent for confirmatory DNA testing. Children who were enrolled in Sickle SAFE less than two years of age were excluded from the PPSV23 and TCD analyses. A total of 141 children were born with SCD and enrolled in Sickle SAFE for at least one year between July 1 2009 and June 30 2015. The majority (56.7%) had HbSS, 32.6% had HbSC, 9.9% were compound heterozygotes for HbS and beta thalassemia and the remaining 0.7% had another sickle hemoglobinopathy. The mean length of follow-up was 2.7 ± 1.0 years. 55.3% were female and 78.7% were African American. 87.2% were publicly insured. Mean age for all patients born with SCD to have confirmatory testing was significantly shorter when confirmatory DNA testing was sent for all affected infants compared to when it was limited to only infants with HbFS [40.3 ±14.1 days (2009-2012) vs. 127.8 ± 173.1 days (2013-2015), p= 1.5E-6]. While the age at confirmatory testing did not differ for infants with HbFS results between the two periods [45.9 ± 14.1 days (2009-2012) vs. 45.8 ± 14.0 days (2013-2015), p=0.98], infants with results other than HbFS were significantly older when confirmatory testing was performed after the process change in 2013 [40.3 ± 14.1 days (2009-2012) vs. 225.3 ± 221.4 days (2013-2015), p=2.6E-6]. Mean age at which genetic counseling was offered to all families with affected children was 26.8 ± 9.9 (range 9-60) days. Mean age at receipt of first dose of penicillin was 28.6 ± 15.0 (range 5-62) days for infants with HbFS, and 29.5 ± 20.1 (range 5-142) days for those with other sickle hemoglobinopathies (p=0.78). 86.5% of enrollees received at least one influenza vaccine while 95.0% had received at least one dose of PCV. Over two-thirds (69.1%) of children with HbFS had TCD screening between the ages of two and three years. 77.3% of Sickle SAFE enrollees who were followed for more than 2 years received PPSV23. Newborn screening for SCD allows for supportive care aimed at reducing morbidity and mortality. Reflex DNA confirmatory testing is an important part of this quality care, regardless of sickle genotype, and our data shows that confirmatory testing is delayed when it is not reflexively performed for all affected infants. The intensive follow-up provided through the Sickle SAFE program increases adherence to quality standards for comprehensive care, as evidenced by a higher rate of TCD screening compared to published data. Education of state departments of health for improved funding and support of programs like Sickle SAFE may help to improve outcomes for affected children. Disclosures No relevant conflicts of interest to declare.

scholarly journals Post-Analytical Tools for the Triage of Newborn Screening Results in Follow-up Can Reduce Confirmatory Testing and Guide Performance Improvement

2020 ◽  
Vol 6 (1) ◽  
pp. 20 ◽  
Author(s):  
Patricia L. Hall ◽  
Angela Wittenauer ◽  
Arthur Hagar
Keyword(s):  
Newborn Screening ◽  
Performance Improvement ◽  
Dehydrogenase Deficiency ◽  
Risk Level ◽  
True Positive ◽  
Inherited Disease ◽  
Confirmatory Testing ◽  
Chain Acyl ◽  
Analytical Tools

Georgia uses post-analytical tools through Collaborative Laboratory Integrated Reports (CLIR) to triage abnormal newborn screening (NBS) results for follow-up. Condition specific tools are used to assign each case a risk level, which is used to guide follow-up recommendations. Follow-up recommendations include assessment by the child’s primary care provider as well as testing, either a repeat NBS or confirmatory testing. Triaging abnormal cases using these tools has been advantageous in managing the workflow for the follow-up team, as well as prioritizing cases that appropriately require more attention and resources. The initial goal in utilizing these tools was to reduce the amount of confirmatory testing, particularly for disorders where there are many false positives. We assessed the performance of these tools retrospectively for three of the most commonly detected conditions by tandem mass spectrometry in Georgia: phenylketonuria, medium chain acyl-CoA dehydrogenase deficiency and very long chain dehydrogenase deficiency. The post-analytical tools appropriately assigned all true positive cases to the higher levels of follow-up testing and reduced the level of intervention for a significant number of cases as well. Based on the experience gained from our utilization of the tools in the follow-up program, we are well situated to move forward with using the tools in a more prospective manner, and reduce the number of cases that will be reported, rather than just assigning resources appropriately at follow-up. Post-analytical tools are an improvement over trying to capture the variation in the newborn population using multiple cutoffs. It also easily identifies significant abnormalities that are unrelated to inherited disease, such as large amino acid elevations due to total parenteral nutrition.

scholarly journals Identification and genomic characterization of a novel human torque teno virus of 3.2 kb

2007 ◽  
Vol 88 (7) ◽  
pp. 1939-1944 ◽  
Author(s):  
Masashi Ninomiya ◽  
Tsutomu Nishizawa ◽  
Masaharu Takahashi ◽  
Felipe R. Lorenzo ◽  
Tooru Shimosegawa ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Torque Teno Virus ◽  
The Novel ◽  
Entire Genome ◽  
Human Sera ◽  
Genomic Characterization ◽  
Novel Virus ◽  
Entire Genomic Sequence ◽  
Genomic Length

In the process of searching for the recently described small anelloviruses 1 and 2 (SAVs) with the genomic DNA length of 2.2 or 2.6 kb in human sera, we isolated a novel virus with its genomic organization resembling those of torque teno virus (TTV) of 3.8–3.9 kb and torque teno mini virus (TTMV) of 2.8–2.9 kb. The entire genomic sequence of three isolates (MD1-032, MD1-073 and MD2-013), which comprised 3242–3253 bases and exhibited 76–99 % identities with the SAVs within the overlapping sequence, was determined. Although the MD1-032, MD1-073 and MD2-013 isolates differed by 10–28 % from each other over the entire genome, they segregated into the same cluster and were phylogenetically distinguishable from all reported TTVs and TTMVs. These results suggest that SAVs are deletion mutants of the novel virus with intermediate genomic length between those of TTV and TTMV and that the novel virus can be classified into a third group of the genus Anellovirus.

The Entire Genomic Sequence and cDNA Expression of Mouse α-Galactosidase A

1996 ◽  
Vol 57 (2) ◽  
pp. 139-148 ◽  
Author(s):  
Richard W. Gotlib ◽  
David F. Bishop ◽  
Anne M. Wang ◽  
Kenneth M. Zeidner ◽  
Yiannis A. Ioannou ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Cdna Expression ◽  
Entire Genomic Sequence
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