{
    "abstract": "Recent findings indicate that infants with spinal muscular atrophy (SMA) treated early through newborn screening (NBS) have better outcomes. This study aimed to investigate the long-term outcomes of a 5-year SMA NBS program in Taiwan.\nFrom September 2017 to August 2022, two NBS centers screened patients for SMN1 homozygous deletion using quantitative real-time polymerase chain reaction (RT-PCR) or the Sequenom MassARRAY platform and subsequently confirmed the findings using multiplex ligation-dependent probe amplification (MLPA). Implementation of SMA NBS using RT-PCR or MassARRAY platform efficiently led to the detection of neonates with homozygous survival motor neuron 1 (SMN1) deletions at a median age of 9 (range 4-14) days. Among the 446,966 newborns screened, 22 were detected to have a homozygous deletion of SMN1, followed by MLPA confirmation. One patient initially showed negative screening results but was later confirmed to have a compound heterozygous mutation. Among the 23 confirmed cases, 8 patients had two SMN2 copies (all classified as SMA type 1), 11 patients had three SMN2 copies (including 4 with SMA type 1, 2 with SMA type 2, 3 with SMA type 3, and 2 asymptomatic cases), and 4 patients had four SMN2 copies (all asymptomatic). The mean (median) follow-up duration for 19 survivors was 4.2 (5.0) years. All patients with two SMN2 copies developed symptoms within 62 days; those with three SMN2 copies experienced disease onset within 1\u00a0year. After diagnosis, most patients were on a watch and wait to receive disease-modifying therapy (DMT) due to initial lack of insurance coverage and limitations on indications after coverage was granted. Of the 19 children who received DMT, the outcomes included 12 walkers, 1 walker requiring support, 3 sitters, 1 non-sitter, and 2 patients with SMA type 1b with two SMN2 copies who succumbed to acute respiratory failure.\nThis 5-year SMA NBS study using RT-PCR or the MassARRAY platform, along with an extended follow-up, demonstrates that early diagnosis and prompt treatment can enhance SMA clinical outcomes and change its natural progression in the therapeutic era. Infants with NBS who received presymptomatic DMT had better clinical outcomes than those who received symptomatic DMT.",
    "authors": [
        {
            "affiliation": "Department of Pediatrics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.\nDepartment of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.\nTranslational Research Center of Neuromuscular Diseases, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.",
            "firstname": "Chen-Hua",
            "initials": "CH",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.\nSchool of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.",
            "firstname": "Ting-Rong",
            "initials": "TR",
            "lastname": "Hsu"
        },
        {
            "affiliation": "Neonatal Screening Center, The Chinese Foundation of Health, Taipei, Taiwan.",
            "firstname": "Mei-Ying",
            "initials": "MY",
            "lastname": "Liu"
        },
        {
            "affiliation": "Neonatal Screening Center, Taipei Institute of Pathology, Taipei, Taiwan.",
            "firstname": "Li-Yun",
            "initials": "LY",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Pediatric Neurology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.",
            "firstname": "I-Jun",
            "initials": "IJ",
            "lastname": "Chou"
        },
        {
            "affiliation": "Department of Pediatric Neurology, National Taiwan University Children's Hospital, Taipei, Taiwan.\nDepartment of Pediatrics, and Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.",
            "firstname": "Wang-Tso",
            "initials": "WT",
            "lastname": "Lee"
        },
        {
            "affiliation": "Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.\nTranslational Research Center of Neuromuscular Diseases, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.\nSchool of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.\nGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.",
            "firstname": "Wen-Chen",
            "initials": "WC",
            "lastname": "Liang"
        },
        {
            "affiliation": "Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.\nInstitute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.",
            "firstname": "Inn-Chi",
            "initials": "IC",
            "lastname": "Lee"
        },
        {
            "affiliation": "Neonatal Screening Center, The Chinese Foundation of Health, Taipei, Taiwan.",
            "firstname": "Hsiao-Jan",
            "initials": "HJ",
            "lastname": "Chen"
        },
        {
            "affiliation": "Neonatal Screening Center, The Chinese Foundation of Health, Taipei, Taiwan.",
            "firstname": "Shu-Min",
            "initials": "SM",
            "lastname": "Kao"
        },
        {
            "affiliation": "Neonatal Screening Center, Taipei Institute of Pathology, Taipei, Taiwan.",
            "firstname": "Hui-Chen",
            "initials": "HC",
            "lastname": "Ho"
        },
        {
            "affiliation": "Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.\nInstitute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.",
            "firstname": "Dau-Ming",
            "initials": "DM",
            "lastname": "Niu"
        },
        {
            "affiliation": "Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.\nPreventive Medicine Foundation, Taipei, Taiwan.\nDepartment of Education and Research, Taipei City Hospital, Taipei, Taiwan.",
            "firstname": "Kwang-Jen",
            "initials": "KJ",
            "lastname": "Hsiao"
        },
        {
            "affiliation": "Pediatric Neurology, Changhua Christian Children's Hospital, Changhua, Taiwan.",
            "firstname": "Ming-Yuh",
            "initials": "MY",
            "lastname": "Chang"
        },
        {
            "affiliation": "Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.",
            "firstname": "Hui-Min",
            "initials": "HM",
            "lastname": "Hsieh"
        },
        {
            "affiliation": "Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. yjjong@gap.kmu.edu.tw.\nTranslational Research Center of Neuromuscular Diseases, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. yjjong@gap.kmu.edu.tw.\nGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. yjjong@gap.kmu.edu.tw.\nDepartment of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. yjjong@gap.kmu.edu.tw.\nCenter for Neurotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. yjjong@gap.kmu.edu.tw.\nDepartment of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan. yjjong@gap.kmu.edu.tw.",
            "firstname": "Yuh-Jyh",
            "initials": "YJ",
            "lastname": "Jong"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. The Author(s).",
    "doi": "10.1186/s13023-025-03697-1",
    "journal": "Orphanet journal of rare diseases",
    "keywords": [
        "Clinical outcome",
        "Disease-modifying therapy",
        "Early treatment",
        "Newborn screening",
        "Presymptomatic treatment",
        "Real-world evidence",
        "Spinal muscular atrophy",
        "Survival motor neuron 1 gene",
        "Survival motor neuron 2 gene copies",
        "Symptomatic treatment"
    ],
    "methods": null,
    "publication_date": "2025-04-25",
    "pubmed_id": "40275389\n7813012\n26515624\n17761648\n30219357\n37510282\n28711173\n21364876\n10339583\n11791208\n29433793\n35927425\n33792051\n39189228\n29614695\n32007960\n39973463\n12815596\n16439605\n24613481\n15921037\n19170031\n38107546\n22047105\n25080519\n32878721\n29091570\n32515646\n28757001\n35835557\n35037741\n38587854\n31704158\n35715566\n35715567\n37409780\n29549190\n36669516\n34321343\n38150893\n35673937",
    "results": "From September 2017 to August 2022, two NBS centers screened patients for SMN1 homozygous deletion using quantitative real-time polymerase chain reaction (RT-PCR) or the Sequenom MassARRAY platform and subsequently confirmed the findings using multiplex ligation-dependent probe amplification (MLPA). Implementation of SMA NBS using RT-PCR or MassARRAY platform efficiently led to the detection of neonates with homozygous survival motor neuron 1 (SMN1) deletions at a median age of 9 (range 4-14) days. Among the 446,966 newborns screened, 22 were detected to have a homozygous deletion of SMN1, followed by MLPA confirmation. One patient initially showed negative screening results but was later confirmed to have a compound heterozygous mutation. Among the 23 confirmed cases, 8 patients had two SMN2 copies (all classified as SMA type 1), 11 patients had three SMN2 copies (including 4 with SMA type 1, 2 with SMA type 2, 3 with SMA type 3, and 2 asymptomatic cases), and 4 patients had four SMN2 copies (all asymptomatic). The mean (median) follow-up duration for 19 survivors was 4.2 (5.0) years. All patients with two SMN2 copies developed symptoms within 62 days; those with three SMN2 copies experienced disease onset within 1\u00a0year. After diagnosis, most patients were on a watch and wait to receive disease-modifying therapy (DMT) due to initial lack of insurance coverage and limitations on indications after coverage was granted. Of the 19 children who received DMT, the outcomes included 12 walkers, 1 walker requiring support, 3 sitters, 1 non-sitter, and 2 patients with SMA type 1b with two SMN2 copies who succumbed to acute respiratory failure.",
    "title": "Newborn screening facilitates early theranostics and improved spinal muscular atrophy outcome: five-year real-world evidence from Taiwan.",
    "xml": "<Element 'PubmedArticle' at 0x7885034035b0>"
}