A Comparative Effectiveness Study of Newborn Screening Methods for Four Lysosomal Storage Disorders

Sanders, Karen A.; Gavrilov, Dimitar; Oglesbee, Devin; Raymond, Kimiyo; Tortorelli, Silvia; Hopwood, John J.; Lorey, Fred; Majumdar, Ramanath; Kroll, Charles; McDonald, Amber; Lacey, Jean M.; Turgeon, Coleman T.; Tucker, Justin N.; Tang, Hao; Currier, Robert; Isaya, Grazia; Rinaldo, Piero; Matern, Dietrich

doi:10.3390/ijns6020044

Cited by 26 publications

(28 citation statements)

References 53 publications

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“…In a previous Italian study, three of six positive males carried this variant [33], and a similar frequency was found in Austria where it was found in three of six positive males [26]. Moreover, more recently, a California NBS study also reported a high frequency of the p.Ala143Thr variant among positive newborns (22/50) [39]. This variant, previously associated with both classic [55] and later-onset phenotype [56], was subsequently considered benign [53,57].…”

Section: Interpretation Of Genetic Variantssupporting

confidence: 61%

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Gragnaniello¹,

Polo²,

Giuliani³

et al. 2021

Biomolecules

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Fabry disease (FD) is a progressive multisystemic lysosomal storage disease. Early diagnosis by newborn screening (NBS) may allow for timely treatment, thus preventing future irreversible organ damage. We present the results of 5.5 years of NBS for FD by α-galactosidase A activity and globotriaosylsphingosine (lyso-Gb3) assays in dried blood spot through a multiplexed MS/MS assay. Furthermore, we report our experience with long-term follow-up of positive subjects. We screened more than 170,000 newborns and 22 males were confirmed to have a GLA gene variant, with an incidence of 1:7879 newborns. All patients were diagnosed with a variant previously associated with the later-onset phenotype of FD or carried an unclassified variant (four patients) or the likely benign p.Ala143Thr variant. All were asymptomatic at the last visit. Although lyso-Gb3 is not considered a reliable second tier test for newborn screening, it can simplify the screening algorithm when its levels are elevated at birth. After birth, plasma lyso-Gb3 is a useful marker for non-invasive monitoring of all positive patients. Our study is the largest reported to date in Europe, and presents data from long-term NBS for FD that reveals the current incidence of FD in northeastern Italy. Our follow-up data describe the early disease course and the trend of plasma lyso-Gb3 during early childhood.

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Section: Interpretation Of Genetic Variantssupporting

confidence: 61%

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Gragnaniello¹,

Polo²,

Giuliani³

et al. 2021

Biomolecules

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“…Of these, one was confirmed as severe MPS I, 13 newborns had pseudo-deficiency alleles, three newborns had variants of unknown significance, and two had heterozygous pathogenic variants [ 27 ]. Other reports in a recent special issue: ‘CLIR applications for Newborn Screening’ in this journal confirm its value in significantly reducing referral rates [ 36 , 37 ]. Retrospective application of CLIR, at least, should be considered a useful exercise for programs screening for MPS I and other LSDs to determine whether initial screen positives could be reduced prior to second-tier testing.…”

Section: Prospective Screening Results From States Using Dmfmentioning

confidence: 74%

Digital Microfluidics in Newborn Screening for Mucopolysaccharidoses: A Progress Report

Washburn

Millington

2020

IJNS

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Newborn screening (NBS) for mucopolysaccharidosis type I (MPS I, Hurler syndrome) is currently conducted in about two-fifths of the NBS programs in the United States and in a few other countries. Screening is performed by measurement of residual activity of the enzyme alpha-l-iduronidase in dried blood spots using either tandem mass spectrometry or digital microfluidic fluorometry (DMF). In this article, we focus on the development and practical experience of using DMF to screen for MPS I in the USA. By means of their responses to a questionnaire, we determined for each responding program that is screening for MPS I using DMF the screen positive rate, follow-up methods, and classification of confirmed cases as either severe or attenuated. Overall, the results show that at the time of reporting, over 1.3 million newborns in the US were screened for MPS I using DMF, 2094 (0.173%) of whom were screen positive. Of these, severe MPS I was confirmed in five cases, attenuated MPS I was confirmed in two cases, and undetermined phenotype was reported in one case. We conclude that DMF is an effective and economical method to screen for MPS I and recommend second-tier testing owing to high screen positive rates. Preliminary results of NBS for MPS II and MPS III using DMF are discussed.

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“… 39–46 Newborn screening programmes also have very low success rates for GD, so they do not appear to be cost-effective outside high-risk populations, with too many probands to identify a very small number of subjects, regardless of the used test (enzyme activity by microfluidics or mass spectrometry, combined with biomarkers or mass genetic analysis). 47 Newborn screening programs are also controversial because of the detection of potentially asymptomatic or oligosymptomatic cases or a high number of false positives, which may have ethical repercussions in terms of parental stress, overmedication or others. This type of search is more applicable in populations with a high prevalence of cases or in family studies.…”

Section: Discussionmentioning

confidence: 99%

“… 46 There is much controversy over the detection of false positives. 47 This approach is controversial because the incidence of cases in general population is low (~1/100,000 live births) in different populations and its application is only promoted in those communities with a high incidence of cases, such as in the Ashkenazi Jewish population, where the incidence is 1/850 births. Recently, the use of genetic analysis panels has been explored.…”

Section: Haematological Manifestations and Screening Programmesmentioning

confidence: 99%

Novel Management and Screening Approaches for Haematological Complications of Gaucher’s Disease

Giraldo¹,

Andrade‐Campos²

2021

JBM

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Purpose Gaucher disease (GD) is the most common lysosomal storage disorder. The principal manifestations for its diagnosis and further monitoring include haematological manifestations such as anaemia, thrombocytopaenia, spleen enlargement, and bleeding disorders, among others. This review aims to summarise and update the role of haematological complications in GD diagnosis and follow-up, describe their management strategies, and to use these indicators as part of the diagnostic approach. Materials and Methods A systematic review following the recommendations of PRISMA-P 2020 was carried out. Publications indexed in the databases PubMed, Embase, Science Open, Mendeley, and Web of Science were electronically searched by three independent reviewers, and publications up to June 2021 were accessed. A total of 246 publications were initially listed, of which 129 were included for further review and analysis. Case reports were considered if they were representative of a relevant hematologic complication. Results From the first review dated in 1974 to the latest publication in 2021, including different populations confirmed that the haematological manifestations such as thrombocytopaenia and splenomegaly at diagnosis of GD type 1 are the most frequent features of the disease. The incorporation of haematological parameters to diagnosis strategies increases their cost-effectiveness. Hematologic parameters are part of the scoring system for disease assessment and the evaluation of therapeutic outcomes, providing reliable and accessible data to improve the management of GD. However, cytopaenia, underlying coagulation disorders, and platelet dysfunction need to be addressed, especially during pregnancy or surgery. Long-term haematological complications include the risk of neoplasia and immune impairment, an area of unmet need that is currently under research. Conclusion Haematological features are key for GD suspicion, diagnosis, and management. Normalization of hematological parameters is achieved with the treatment; however, there are unmet needs such as the underlying inflammatory status and the long-term risk of hematologic neoplasia.

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A Comparative Effectiveness Study of Newborn Screening Methods for Four Lysosomal Storage Disorders

Cited by 26 publications

References 53 publications

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Digital Microfluidics in Newborn Screening for Mucopolysaccharidoses: A Progress Report

Novel Management and Screening Approaches for Haematological Complications of Gaucher’s Disease

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