纽约州脊髓性肌萎缩症新生儿筛查：头 3 年的临床结果。

Newborn Screening for Spinal Muscular Atrophy in New York State: Clinical Outcomes From the First 3 Years.

机构信息

From the Department of Neurology (B.H.L., S.D., E.C.), University of Rochester NY; Columbia University (C.A.C., K.E., A.L.), Department of Neurology, Division of Child Neurology, New York, NY; Newborn Screening Program (D.M.K., M.C., C.A.S.-M., C.F.S.), Division of Genetics, Wadsworth Center, New York State Department of Health, Albany; Cohen Children's Medical Center (O.I., E.L., K.H.), New Hyde Park, NY; Montefiore Medical Center (L.D.), Bronx, NY; Stony Brook University (S.O.T.), Department of Neurology, Stony Brook, NY; SUNY Downstate Medical Center (Y.A.), Brooklyn, NY; SUNY Upstate Medical Center (A.S.), Department of Neurology, Syracuse, NY; Albany Medical Center (C.K.), Department of Pediatrics, Genetics and Metabolism, NY; and University of Buffalo (O.F.), NY.

出版信息

Neurology. 2022 Oct 3;99(14):e1527-e1537. doi: 10.1212/WNL.0000000000200986.

DOI:10.1212/WNL.0000000000200986

PMID:35835557

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9576300/

Abstract

BACKGROUND AND OBJECTIVES

Spinal muscular atrophy (SMA) was added to the Recommended Uniform Screening Panel in July 2018 largely on the basis of the availability and efficacy of newly approved disease-modifying therapies. New York State (NYS) started universal newborn screening for SMA in October 2018. The authors report the findings from the first 3 years of screening.

METHODS

Statewide neonatal screening was conducted using DNA extracted from dried blood spots using a real-time quantitative PCR assay. Retrospective follow-up data were collected from 9 referral centers across the state on 34 infants.

RESULTS

In the first 3 years since statewide implementation, nearly 650,000 infants have been screened for SMA. Thirty-four babies screened positive and were referred to a neuromuscular specialty care center. The incidence remains lower than previously predicted. The majority (94%), including all infants with 2-3 copies of survival motor neuron ( 2, have received treatment. Among treated infants, the overwhelming majority (94%; 30/32) have received gene replacement. All infants in this cohort with 3 copies of are clinically asymptomatic posttreatment based on early clinical follow-up data. Infants with 2 copies of are more variable in their outcomes. Electrodiagnostic outcomes data obtained from a subgroup of patients (n = 11) demonstrated either improvement or no change in compound muscle action potential (CMAP) amplitude at last clinical follow-up compared with pretreatment baseline. Most infants were treated before 6 weeks of age (median = 34.5 days of life; range 11-180 days). Delays and barriers to treatment identified by treating clinicians followed 2 broad themes: medical and nonmedical. Medical delays most commonly reported were the presence of AAV9 antibodies and elevated troponin I levels. Nonmedical barriers included delays in obtaining insurance and insurance policies regarding specific treatment modalities.

DISCUSSION

The findings from the NYS cohort of newborn screen-identified infants are consistent with other reports of improved outcomes from early diagnosis and treatment. Additional biomarkers of motor neuron health including EMG can potentially be helpful in detecting preclinical decline.

摘要

背景与目的

脊髓性肌萎缩症（SMA）于 2018 年 7 月被纳入推荐的统一筛查方案，主要是基于新批准的疾病修正治疗方法的有效性和可用性。纽约州（NYS）于 2018 年 10 月开始对 SMA 进行普遍的新生儿筛查。作者报告了筛查的前 3 年的结果。

方法

全州范围内的新生儿筛查使用从干燥血斑中提取的 DNA，使用实时定量 PCR 检测方法进行。从全州 9 个转诊中心收集了 34 名婴儿的回顾性随访数据。

结果

在全州实施后的前 3 年中，近 65 万名婴儿接受了 SMA 筛查。34 名婴儿筛查阳性，并被转介到神经肌肉专科治疗中心。发病率仍然低于之前的预测。大多数（94%，包括所有有 2-3 份生存运动神经元的婴儿（SMN1），接受了治疗。在接受治疗的婴儿中，绝大多数（94%，30/32）接受了基因替代治疗。根据早期临床随访数据，该队列中的所有 3 份 SMN1 婴儿在治疗后均无临床症状。有 2 份 SMN1 婴儿的结果更为多变。从一组患者（n=11）获得的电诊断结果数据显示，与治疗前基线相比，最后一次临床随访时复合肌肉动作电位（CMAP）幅度要么改善，要么不变。大多数婴儿在 6 周龄之前接受治疗（中位数=34.5 天的生命；范围 11-180 天）。治疗医生发现的治疗延误和障碍有 2 个广泛的主题：医疗和非医疗。最常见的医疗延误报告是存在 AAV9 抗体和肌钙蛋白 I 水平升高。非医疗障碍包括获得保险和保险政策方面的延误，涉及特定的治疗方法。