Shaff Austin, Basheeruddin Khaja, Bekri Soumeya, Brown Heather A, Church Heather J, Gianares Justin, Hong Xinying, Jones Simon A, Kappell Tate, Kubaski Francyne, Oliva Petra, Orsini Joseph, Tebani Abdellah, Wu Teresa H Y, Lalic Gojko, Gelb Michael H
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
Illinois Department of Public Health, Chicago, IL 60612, United States of America.
Mol Genet Metab. 2025 Jul;145(3):109138. doi: 10.1016/j.ymgme.2025.109138. Epub 2025 May 18.
Ex vivo gene therapy combined with haemapoietic stem cell transplant has recently been approved in Europe and the USA for treatment of metachromatic leukodystrophy (MLD). Since treatment is only efficacious if carried out in the pre-symptomatic or minimally-symptomatic phases, newborn screening (NBS) for MLD is warranted. MLD NBS is being developed worldwide through the International MLD Newborn Screening Alliance. Screening is carried out by measurement of the elevation of two sulfatide molecular species, 16: 0- and 16:1-OH-sulfatide in dried blood spots (DBS) followed by second-tier measurement of arylsulfatase A (ARSA) enzymatic activity in the same DBS. After 2-3 years of NBS assay development including pilot studies, members of the International MLD Newborn Screening Alliance arrived at a consensus set of assay protocols. In this article, we provide these protocols with full details so that the methods can be readily adopted by additional NBS laboratories. We also provide the full details of preparation of the required reagents.
体外基因治疗联合造血干细胞移植最近在欧洲和美国已被批准用于治疗异染性脑白质营养不良（MLD）。由于该治疗仅在症状前或症状轻微阶段进行才有效，因此有必要对MLD进行新生儿筛查（NBS）。全球正在通过国际MLD新生儿筛查联盟开展MLD的NBS工作。筛查通过测量干血斑（DBS）中两种硫脂分子种类（16:0 - 和16:1 - OH - 硫脂）的升高情况进行，随后在同一DBS中进行芳基硫酸酯酶A（ARSA）酶活性的二线测量。经过包括试点研究在内的2 - 3年NBS检测方法开发，国际MLD新生儿筛查联盟的成员达成了一套共识检测方案。在本文中，我们提供这些方案的完整细节，以便其他NBS实验室能够轻松采用这些方法。我们还提供所需试剂制备的完整细节。
