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Light and Shadows in Newborn Screening for Lysosomal Storage Disorders: Eight Years of Experience in Northeast Italy. 新生儿溶酶体贮积症筛查中的光明与阴影:意大利东北部八年的经验。
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-12-25 DOI: 10.3390/ijns10010003
Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Andrea Puma, Christian Loro, Elena Porcù, Maria Stornaiuolo, Paolo Miglioranza, Leonardo Salviati, Alessandro P Burlina, Alberto B Burlina

In the last two decades, the development of high-throughput diagnostic methods and the availability of effective treatments have increased the interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow-up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry disease, Gaucher disease), using the enzyme activity assay by tandem mass spectrometry, and biomarker quantification as a second-tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive predictive value 40%), with an overall incidence of 1:4874. Of these, three patients with infantile-onset Pompe disease, two with neonatal-onset Gaucher disease and four with mucopolysaccharidosis type I were immediately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrates the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient outcomes. Challenges such as false-positive rates, the diagnosis of variants of uncertain significance or late-onset forms and the lack of treatment for neuronopathic forms, should be addressed.

在过去二十年中,高通量诊断方法的发展和有效治疗方法的出现提高了人们对新生儿溶酶体储积症筛查的兴趣。然而,要明确风险、益处和挑战,还需要长期的随访经验。我们报告了 8 年来对约 25 万名新生儿进行筛查和随访的经验,这些新生儿筛查出四种溶酶体贮积症(庞贝病、I 型粘多糖病、法布里病和戈谢病),筛查采用串联质谱酶活性检测法,生物标记物定量检测法作为第二级检测。在 126 名阳性新生儿(0.051%)中,有 51 名婴儿被确诊为患者(阳性预测值为 40%),总发病率为 1:4874。其中,3 名婴儿型庞贝病患者、2 名新生儿型戈谢病患者和 4 名 I 型粘多糖病患者立即得到了治疗。此外,还有四名戈谢病患者需要在出生后的头几年接受治疗。我们的研究证明了新生儿溶酶体储积症筛查的可行性和有效性。早期诊断和治疗可为患者带来更好的治疗效果。假阳性率、意义不确定的变异或晚发形式的诊断以及神经病变缺乏治疗等挑战应得到解决。
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引用次数: 0
Incidental Detection of Classical Galactosemia through Newborn Screening for Phenylketonuria: A 10-Year Retrospective Audit to Determine the Efficacy of This Approach 通过新生儿苯丙酮尿症筛查偶然发现典型半乳糖血症:确定该方法有效性的 10 年回顾性审计
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-12-22 DOI: 10.3390/ijns10010002
Nathan W. P. Cantley, R. Barski, Helena Kemp, Sarah L Hogg, Hoi Yee Teresa Wu, Ann Bowron, Catherine Collingwood, Jennifer Cundick, Claire Hart, L. Shakespeare, Mary Anne Preece, Helen Aitkenhead, Sarah Smith, R. Carling, Stuart J Moat
In the UK, Classical Galactosaemia (CG) is identified incidentally from the Newborn Screening (NBS) for phenylketonuria (PKU) using an “Other disorder suspected” (ODS) pathway when phenylalanine (Phe) and tyrosine (Tyr) concentrations are increased. We aimed to determine the efficacy of CG detection via NBS and estimate the incidence of CG in live births in the UK. A survey was sent to all UK NBS laboratories to collate CG cases diagnosed in the UK from 2010 to 2020. Cases of CG diagnosed were determined if detected clinically, NBS, or by family screening, as well as age at diagnosis. Cases referred via the ODS pathway were also collated, including the final diagnosis made. Responses were obtained from 13/16 laboratories. Between 2010 and 2020, a total of 6,642,787 babies were screened, and 172 cases of CG were identified. It should be noted that 85/172 presented clinically, 52/172 were identified by NBS, and 17/172 came from family screening. A total of 117 referrals were made via the ODS pathway, and 45/117 were subsequently diagnosed with CG. Median (interquartile range) age at diagnosis by NBS and clinically was 8 days (7–11) and 10 days (7–16), respectively (Mann–Whitney U test, U = 836.5, p-value = 0.082). The incidence of CG is 1:38,621 live births. The incidence of CG in the UK is comparable with that of other European/western countries. No statistical difference was seen in the timing of diagnosis between NBS and clinical presentation based on the current practice of sampling on day 5. Bringing forward the day of NBS sampling to day 3 would increase the proportion diagnosed with CG by NBS from 52/172 (30.2%) to 66/172 (38.4%).
在英国,当苯丙氨酸(Phe)和酪氨酸(Tyr)浓度升高时,通过 "疑似其他疾病"(ODS)途径进行的苯丙酮尿症(PKU)新生儿筛查(NBS)会偶然发现典型半乳糖血症(CG)。我们的目的是确定通过新生儿筛查检测 CG 的有效性,并估计 CG 在英国活产婴儿中的发病率。我们向英国所有 NBS 实验室发送了一份调查问卷,以整理 2010 年至 2020 年英国确诊的 CG 病例。通过临床、NBS或家庭筛查发现的CG病例以及确诊时的年龄均可确定。此外,还整理了通过 ODS 途径转诊的病例,包括最终诊断结果。13/16 个实验室做出了回复。2010 年至 2020 年间,共有 6,642,787 名婴儿接受了筛查,发现了 172 例 CG。值得注意的是,85/172 例是临床表现,52/172 例是通过 NBS 确定,17/172 例来自家庭筛查。共有 117 例通过 ODS 途径转诊,其中 45/117 例随后被确诊为 CG。通过 NBS 和临床诊断的中位年龄(四分位数间距)分别为 8 天(7-11)和 10 天(7-16)(曼-惠特尼 U 检验,U = 836.5,P 值 = 0.082)。CG的发病率为1:38,621。英国 CG 的发病率与其他欧洲/西方国家相当。根据目前第 5 天采样的做法,NBS 和临床表现之间的诊断时间没有统计学差异。将 NBS 采样日期提前到第 3 天将使 NBS 诊断出 CG 的比例从 52/172 (30.2%) 增加到 66/172 (38.4%)。
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引用次数: 0
Droplet Digital PCR (ddPCR) Does Not Enhance the Sensitivity of Detection of Cytomegalovirus (CMV) DNA in Newborn Dried Blood Spots Evaluated in the Context of Newborn Congenital CMV (cCMV) Screening 在新生儿先天性巨细胞病毒 (cCMV) 筛查中评估液滴数字 PCR (ddPCR) 是否能提高新生儿干血斑中巨细胞病毒 (CMV) DNA 的检测灵敏度
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-12-20 DOI: 10.3390/ijns10010001
Nelmary Hernandez-Alvarado, Craig J. Bierle, M. Schleiss
Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such as PCR testing of newborn dried blood spots (DBS). This study aimed to evaluate the sensitivity of droplet digital PCR (ddPCR) compared to quantitative real-time PCR to detect CMV DNA in newborn DBS. The limit of detection of various ddPCR primer/probe combinations (singleplex UL55-HEX, singleplex UL83-FAM, and multiplex UL55-HEX/UL83-FAM) was evaluated using the National Institute of Standards and Technology’s (NIST) CMV quantitative standard. Singleplex UL55-HEX ddPCR exhibited the lowest limit of detection among the primer/probe combinations tested for ddPCR. UL55 ddPCR was then compared to real-time PCR in 49 infants with confirmed cCMV identified through newborn screening for CMV in saliva swabs and confirmed by a urine test. The results showed that ddPCR was only positive for 59% (29 out of 49) of the cCMV infants, while real-time PCR was positive for 80% (39 out of 49). Due to its lower sensitivity and throughput, ddPCR may not be suitable for cCMV newborn screening.
先天性巨细胞病毒(cCMV)感染是导致全球儿童感音神经性听力损失(SNHL)和神经发育障碍的主要原因。美国和加拿大的一些地区已开始普及新生儿巨细胞病毒筛查,这需要采用分子诊断技术来识别巨细胞病毒,如新生儿干血斑(DBS)的 PCR 检测。本研究旨在评估与定量实时 PCR 相比,液滴数字 PCR(ddPCR)检测新生儿干血斑中 CMV DNA 的灵敏度。使用美国国家标准与技术研究院(NIST)的 CMV 定量标准评估了各种 ddPCR 引物/探针组合(单倍 UL55-HEX、单倍 UL83-FAM 和多倍 UL55-HEX/UL83-FAM)的检测限。在进行 ddPCR 测试的引物/探针组合中,单重 UL55-HEX ddPCR 的检测限最低。随后,UL55 ddPCR 与实时 PCR 对 49 名通过新生儿唾液拭子中的 CMV 筛查发现并通过尿液检测确诊为 cCMV 的婴儿进行了比较。结果显示,ddPCR 仅对 59% 的 cCMV 婴儿(49 人中有 29 人)呈阳性,而实时 PCR 则对 80% 的 cCMV 婴儿(49 人中有 39 人)呈阳性。由于 ddPCR 的灵敏度和通量较低,因此可能不适合用于 cCMV 新生儿筛查。
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引用次数: 0
Newborn Screening for Severe Combined Immunodeficiency: Lessons Learned from Screening and Follow-Up of the Preterm Newborn Population. 新生儿严重联合免疫缺陷筛查:早产新生儿筛查和随访的经验教训。
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-12-15 DOI: 10.3390/ijns9040068
Amy Gaviglio, Michael Lasarev, Ruthanne Sheller, Sikha Singh, Mei Baker

Newborn screening (NBS) for Severe Combined Immunodeficiency (SCID) by measurement of T-cell receptor excision circles (TRECs) successfully identifies newborns with SCID and severe T-cell lymphopenia, as intended. At the same time, NBS programs face the challenge of false positive results, with a disproportionately high number in the premature newborn population. This study evaluates TREC values and SCID screening outcomes in premature newborns and elucidates evidence-based SCID screening practices that reduce unnecessary follow-up activities in this population. De-identified individual SCID newborn screening data and aggregate SCID screening data were obtained from seven states across the US for babies born between 2018 and 2020. Relevant statistics were performed on data pooled from these states to quantify screening performance metrics and clinical impact on various birth and gestational age categories of newborns. The data were normalized using multiples-of-the-median (MoM) values to allow for the aggregation of data across states. The aggregation of NBS data across a range of NBS programs highlighted the trajectory of TREC values over time, both between and within newborns, and provides evidence for improved SCID screening recommendations in the premature and low birth weight population.

通过测量 T 细胞受体切割圈 (TRECs),新生儿重症联合免疫缺陷 (SCID) 筛查 (NBS) 如期成功识别出患有 SCID 和重症 T 细胞淋巴细胞减少症的新生儿。与此同时,新生儿筛查项目也面临着假阳性结果的挑战,早产新生儿中的假阳性结果比例过高。本研究对早产新生儿的 TREC 值和 SCID 筛查结果进行了评估,并阐明了以证据为基础的 SCID 筛查方法,以减少该人群中不必要的随访活动。研究人员从全美七个州获得了 2018 年至 2020 年间出生婴儿的去身份化个体 SCID 新生儿筛查数据和 SCID 筛查汇总数据。对这些州的汇总数据进行了相关统计,以量化筛查绩效指标以及对不同出生和胎龄类别新生儿的临床影响。数据采用中位数倍数(MoM)值进行归一化处理,以便汇总各州的数据。对一系列 NBS 项目的 NBS 数据进行汇总后,突显了 TREC 值在新生儿之间和新生儿内部随时间变化的轨迹,并为改进早产儿和低出生体重儿的 SCID 筛查建议提供了证据。
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引用次数: 0
Newborn Genetic Screening—Still a Role for Sanger Sequencing in the Era of NGS 新生儿基因筛查--桑格测序在 NGS 时代仍有用武之地
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-12-07 DOI: 10.3390/ijns9040067
Silje Hogner, E. Lundman, J. Strand, M. Ytre-Arne, T. Tangeraas, A. Stray-Pedersen
In the Norwegian newborn screening (NBS) program, genetic testing has been implemented as a second or third tier method for the majority of NBS disorders, significantly increasing positive predictive value (PPV). DNA is extracted from dried blood spot (DBS) filter cards. For monogenic disorders caused by variants in one single gene or a few genes only, Sanger sequencing has been shown to be the most time- and cost-efficient method to use. Here, we present the Sanger sequencing method, including primer sequences and the genetic test algorithms, currently used in the Norwegian newborn screening program.
在挪威新生儿筛查(NBS)项目中,基因检测已被作为大多数NBS疾病的第二或第三级方法实施,显著提高了阳性预测值(PPV)。DNA是从干血斑(DBS)过滤卡中提取的。对于由单个基因或少数基因变异引起的单基因疾病,Sanger测序已被证明是最省时和最具成本效益的方法。在这里,我们提出了Sanger测序方法,包括引物序列和基因检测算法,目前用于挪威新生儿筛查计划。
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引用次数: 0
A False-Negative Newborn Screen for Tyrosinemia Type 1—Need for Re-Evaluation of Newborn Screening with Succinylacetone 酪氨酸血症 1 型新生儿筛查假阴性--重新评估琥珀酰丙酮新生儿筛查的必要性
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-12-04 DOI: 10.3390/ijns9040066
A. Dijkstra, Kimber Evers-van Vliet, M. Heiner-Fokkema, F. Bodewes, Dennis K. Bos, J. Zsiros, Koen J. van Aerde, K. Koop, F. V. van Spronsen, Charlotte M. A. Lubout
Undiagnosed and untreated tyrosinemia type 1 (TT1) individuals carry a significant risk for developing liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Elevated succinylacetone (SA) is pathognomonic for TT1 and therefore often used as marker for TT1 newborn screening (NBS). While SA was long considered to be elevated in every TT1 patient, here we present a recent false-negative SA TT1 screen. A nine-year-old boy presented with HCC in a cirrhotic liver. Additional tests for the underlying cause unexpectedly revealed TT1. Nine years prior, the patient was screened for TT1 via SA NBS with a negative result: SA 1.08 µmol/L, NBS cut-off 1.20 µmol/L. To our knowledge, this report is the first to describe a false-negative result from the TT1 NBS using SA. False-negative TT1 NBS results may be caused by milder TT1 variants with lower SA excretion. Such patients are more likely to be missed in NBS programs and can be asymptomatic for years. Based on our case, we advise TT1 to be considered in patients with otherwise unexplained liver pathology, including fibrosis, cirrhosis and HCC, despite a previous negative TT1 NBS status. Moreover, because the NBS SA concentration of this patient fell below the Dutch cut-off value (1.20 µmol/L at that time), as well as below the range of cut-off values used in other countries (1.29–10 µmol/L), it is likely that false-negative screening results for TT1 may also be occurring internationally. This underscores the need to re-evaluate TT1 SA NBS programs.
未确诊和未经治疗的1型酪氨酸血症(TT1)患者发生肝纤维化、肝硬化和肝细胞癌(HCC)的风险很大。琥珀酰丙酮(SA)升高是TT1的病理特征,因此常被用作TT1新生儿筛查(NBS)的标志物。虽然长期以来认为SA在每个TT1患者中升高,但在这里,我们提出了最近的TT1假阴性SA筛查。一个九岁男孩在肝硬化中出现HCC。针对潜在原因的其他测试意外显示为TT1。9年前,患者通过SA NBS筛查TT1,结果为阴性:SA 1.08µmol/L, NBS截止值1.20µmol/L。据我们所知,该报告是第一个使用SA描述TT1 NBS假阴性结果的报告。TT1 NBS结果假阴性可能是由较轻的TT1变异与较低的SA排泄引起的。这些患者更有可能在NBS计划中被遗漏,并且可能多年无症状。根据我们的病例,我们建议在有其他原因不明的肝脏病理(包括纤维化、肝硬化和HCC)的患者中考虑TT1,尽管之前的TT1 NBS状态为阴性。此外,由于该患者的NBS SA浓度低于当时荷兰的临界值(1.20µmol/L),也低于其他国家使用的临界值范围(1.29-10µmol/L),因此国际上也可能出现TT1筛查假阴性结果。这强调了重新评估TT1 SA NBS计划的必要性。
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引用次数: 0
Cystic Fibrosis Cases Missed by Newborn Bloodspot Screening-Towards a Consistent Definition and Data Acquisition. 新生儿血斑筛查漏诊的囊性纤维化病例--实现一致的定义和数据采集。
IF 3.5 Q1 GENETICS & HEREDITY Pub Date : 2023-11-21 DOI: 10.3390/ijns9040065
Anne Munck, Kevin W Southern, Jared Murphy, Karin M de Winter-de Groot, Silvia Gartner, Bülent Karadag, Nataliya Kashirskaya, Barry Linnane, Marijke Proesmans, Dorota Sands, Olaf Sommerburg, Carlo Castellani, Jürg Barben

Repeated European surveys of newborn bloodspot screening (NBS) have shown varied strategies for collecting missed cases, and information on data collection differs among countries/regions, hampering data comparison. The ECFS Neonatal Screening Working Group defined missed cases by NBS as either false negatives, protocol-related, concerning analytical issues, or non-protocol-related, concerning pre- and post-analytical issues. A questionnaire has been designed and sent to all key workers identified in each NBS programme to assess the feasibility of collecting data on missed cases, the stage of the NBS programme when the system failed, and individual patient data on each missed case.

欧洲反复进行的新生儿血斑筛查(NBS)调查显示,收集漏检病例的策略各不相同,而且各国/各地区的数据收集信息也不尽相同,这妨碍了数据比较。ECFS 新生儿筛查工作组将 NBS 的漏检病例定义为假阴性病例、与分析问题有关的协议相关病例或与分析前后问题有关的非协议相关病例。已设计了一份调查问卷,并发送给每个新生儿筛查计划中确定的所有关键工作人员,以评估收集漏报病例数据的可行性、系统出现故障时新生儿筛查计划所处的阶段以及每个漏报病例的单个患者数据。
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引用次数: 0
Diagnosing X-Linked Adrenoleukodystrophy after Implementation of Newborn Screening: A Reference Laboratory Perspective 新生儿筛查后诊断x连锁肾上腺脑白质营养不良:参考实验室视角
Q1 GENETICS & HEREDITY Pub Date : 2023-11-02 DOI: 10.3390/ijns9040064
Julia Prinzi, Marzia Pasquali, Judith A. Hobert, Rachel Palmquist, Kristen N. Wong, Stephanie Francis, Irene De Biase
Adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, encoding for the adrenoleukodystrophy protein (ALDP), leading to defective peroxisomal β-oxidation of very long-chain and branched-chain fatty acids (VLCFA). ALD manifests in both sexes with a spectrum of phenotypes, but approximately 35% of affected males develop childhood cerebral adrenoleukodystrophy (CCALD), which is lethal without hematopoietic stem cell transplant performed before symptoms start. Hence, ALD was added to the Recommended Uniform Screening Panel after the successful implementation in New York State (2013–2016). To date, thirty-five states have implemented newborn screening (NBS) for ALD, and a few programs have reported on the successes and challenges experienced. However, the overall impact of NBS on early detection of ALD has yet to be fully determined. Here, we conducted a retrospective analysis of VLCFA testing performed by our reference laboratory (ARUP Laboratories, Salt Lake City, UT, USA) over 10 years. Rate of detection, age at diagnosis, and male-to-female ratio were evaluated in patients with abnormal results before and after NBS implementation. After NBS inclusion, a significant increase in abnormal results was observed (471/6930, 6.8% vs. 384/11,670, 3.3%; p < 0.0001). Patients with ALDP deficiency identified via NBS were significantly younger (median age: 30 days vs. 21 years; p < 0.0001), and males and females were equally represented. ALD inclusion in NBS programs has increased pre-symptomatic detection of this disease, which is critical in preventing adrenal crisis as well as the severe cerebral form.
肾上腺脑白质营养不良(ALD)是由编码肾上腺脑白质营养不良蛋白(ALDP)的ABCD1基因的致病性变异引起的,导致过氧化物酶体β-氧化极长链和支链脂肪酸(VLCFA)的缺陷。ALD在两性中均有表现,具有多种表型,但大约35%的受影响男性会出现儿童期脑肾上腺白质营养不良(CCALD),在症状开始前不进行造血干细胞移植是致命的。因此,ALD在纽约州成功实施后(2013-2016年)被添加到推荐统一筛查小组中。迄今为止,35个州已经实施了新生儿ALD筛查(NBS),一些项目已经报告了成功和面临的挑战。然而,NBS对ALD早期发现的总体影响尚未完全确定。在这里,我们对参考实验室(ARUP Laboratories, Salt Lake City, UT, USA) 10年来进行的VLCFA测试进行了回顾性分析。对NBS实施前后结果异常患者的检出率、诊断年龄、男女比例进行评估。纳入NBS后,异常结果显著增加(471/6930,6.8% vs. 384/11,670, 3.3%;p & lt;0.0001)。通过NBS确定的ALDP缺乏症患者明显更年轻(中位年龄:30天vs 21岁;p & lt;0.0001),男女比例相等。将ALD纳入NBS计划增加了该病的症状前检测,这对于预防肾上腺危机和严重的大脑形式至关重要。
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引用次数: 0
NBSTRN Tools to Advance Newborn Screening Research and Support Newborn Screening Stakeholders NBSTRN工具推进新生儿筛查研究和支持新生儿筛查利益相关者
Q1 GENETICS & HEREDITY Pub Date : 2023-10-30 DOI: 10.3390/ijns9040063
Kee Chan, Zhanzhi Hu, Lynn W. Bush, Heidi Cope, Ingrid A. Holm, Stephen F. Kingsmore, Kevin Wilhelm, Curt Scharfe, Amy Brower
Rapid advances in the screening, diagnosis, and treatment of genetic disorders have increased the number of conditions that can be detected through universal newborn screening (NBS). However, the addition of conditions to the Recommended Uniform Screening Panel (RUSP) and the implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here, we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders worldwide. The NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs, including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases, have utilized NBSTRN’s tools and, in turn, contributed research data to further expand and refine these resources. Additionally, we discuss ongoing tool development to facilitate the expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families.
遗传疾病筛查、诊断和治疗方面的快速进展增加了通过新生儿普遍筛查(NBS)可以检测到的疾病数量。然而,在建议统一筛选小组(RUSP)中增加条件和在全国范围内实施筛选一直是一个缓慢的过程,需要数年时间才能完成个别条件。在这里,我们描述了新生儿筛查转化研究网络(NBSTRN)开发和实施的基于网络的工具和资源,以推进新生儿筛查研究并支持全球NBS利益相关者。NBSTRN的工具包括纵向儿科数据资源(LPDR)、国家统计局条件资源(NBS- cr)、国家统计局虚拟存储库(NBS- vr)和伦理、法律和社会问题(ELSI)优势。研究项目,包括代谢信息系统的先天错误(IBEM-IS)、BabySeq、EarlyCheck和家庭叙述用例,都利用了NBSTRN的工具,并反过来贡献了研究数据,以进一步扩展和完善这些资源。此外,我们还讨论了正在进行的工具开发,以促进在日益多样化的人群中扩大遗传病筛查。总之,NBSTRN的工具和资源提供了一个值得信赖的平台,使国家统计局的利益相关者能够推进国家统计局的研究,并改善对患者及其家属的临床护理。
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引用次数: 0
Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity 全日本用(C16 + C18:1)/C2和C14/C3筛查新生儿肉毒碱棕榈酰基转移酶II缺乏症,显示C12/C0指标具有较高的敏感性和特异性
Q1 GENETICS & HEREDITY Pub Date : 2023-10-27 DOI: 10.3390/ijns9040062
Go Tajima, Keiichi Hara, Miyuki Tsumura, Reiko Kagawa, Fumiaki Sakura, Hideo Sasai, Miori Yuasa, Yosuke Shigematsu, Satoshi Okada
Carnitine palmitoyltransferase (CPT) II deficiency is a long-chain fatty acid oxidation disorder. It manifests as (1) a lethal neonatal form, (2) a hypoglycemic form, or (3) a myopathic form. The second form can cause sudden infant death and is more common among Japanese people than in other ethnic groups. Our study group had earlier used (C16 + C18:1)/C2 to conduct a pilot newborn screening (NBS) study, and found that the use of C14/C3 for screening yielded lower rates of false positivity; in 2018, as a result, nationwide NBS for CPT II deficiency started. In this study, we evaluated the utility of these ratios in 71 NBS-positive infants and found that the levels of both C14/C3 and (C16 + C18:1)/C2 in patients overlapped greatly with those of infants without the disease. Among the levels of acylcarnitines with various chain lengths (C18 to C2) and levels of free carnitine (C0) as well as their ratios of various patterns, C12/C0 appeared to be a promising index that could reduce false-positive results without missing true-positive cases detected by current indices. Although some cases of the myopathic form may go undetected even with C12/C0, its use will help prevent life-threatening onset of the hypoglycemic form of CPT II deficiency.
肉毒碱棕榈酰基转移酶(CPT) II缺乏症是一种长链脂肪酸氧化障碍。它表现为(1)新生儿致死型,(2)低血糖型,或(3)肌病型。第二种形式可导致婴儿猝死,在日本人中比在其他民族中更常见。我们的研究组早先曾使用(C16 + C18:1)/C2进行新生儿筛查(NBS)试点研究,并发现使用C14/C3进行筛查产生较低的假阳性率;因此,2018年全国启动了对CPT II缺乏症的国家统计局。在这项研究中,我们评估了71名nbs阳性婴儿的这些比值的效用,发现患者的C14/C3和(C16 + C18:1)/C2水平与未患病婴儿的水平有很大的重叠。在不同链长酰基肉碱(C18 ~ C2)水平和游离肉碱(C0)水平及其各种模式的比值中,C12/C0是一个很有前景的指标,可以减少假阳性结果,而不会遗漏现有指标检测出的真阳性病例。虽然有些病例即使有C12/C0也可能无法检测到肌病形式,但它的使用将有助于预防危及生命的CPT II缺乏症低血糖形式的发作。
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引用次数: 0
期刊
International Journal of Neonatal Screening
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