BACKGROUND The necessity of early treatment for lysosomal storage diseases (LSDs) has triggered the development of newborn screening for LSDs in recent years. Here we report the first 70,000 newborns screened for Mucopolysaccharidosis (MPS) type 4A (Morquio syndrome) and other LSDs by an 8-plex assay including the original 4-plex LSD screening tandem mass spectrometry (MS/MS) assay for Pompe disease, Fabry disease, Gaucher disease, and MPS I disease. METHODS The additional reaction for MPS II, MPS 3B, MPS 4A, and MPS 6 enzymes was performed separately from the 4-plex reaction. The two reactions were quenched and extracted, then combined before carrying out a single 2-min UPLC-MS/MS analysis. RESULTS From Mar. 2018 to Apr. 2019, 73,743 newborns were screened with the 8-plex LSD screening assay. The 8-plex assay revealed a better analytical precision than the previous 4-plex assay possibly because the 8-plex was carried out using UPLC-MS/MS. Six newborns were found to have low MPS-4A enzyme (N-acetylgalactosamine-6-sulfatase) activity and biallelic GALNS pathogenic mutations in trans; these patients are presumably affected with MPS4A, making an incidence of one in 12,291 (95% confident interval (CI): 5633-26,817). One mutation, c.857C > T (p.T286 M) of the GALNS gene, accounted 5 of the 12 mutated alleles. These newborns had immature vertebral bodies at 1 month of age, and one case was treated with elosulfase alfa 2 mg/kg/week starting from 4 months of age. Among other MPSs screened, one case of MPS I, 3 cases of MPS II, and 3 cases of MPS 3B were detected. One case of mucolipidosis type III was also diagnosed. In conjunction with another 9 patients of Pompe disease, Gaucher disease, and classical Fabry disease, making an incidence of LSDs as one in 3206 newborns (95% CI: 2137 - 4811). The one with infantile-onset Pompe disease and the one with Gaucher disease were treated since the age of 8 days and 41 days respectively. CONCLUSIONS Routine newborn screening of MPS 4A and other LSDs were made possible by the 8-plex LSD screening assay. However, detailed phenotype prediction and the time to start treatment will need further elucidation.

中文翻译：

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Morquio 病和其他溶酶体贮积病的新生儿筛查：对 70,000 名新生儿进行 8 重检测的结果。


背景技术近年来，溶酶体贮积病（LSD）早期治疗的必要性引发了新生儿LSD筛查的发展。在这里，我们报告了首批 70,000 名新生儿通过 8 重检测进行了粘多糖贮积症 (MPS) 4A 型（莫基奥综合征）和其他 LSD 筛查，其中包括用于庞贝病、法布里病的原始 4 重 LSD 筛查串联质谱 (MS/MS) 检测病、戈谢病和 MPS I 病。方法 MPS II、MPS 3B、MPS 4A 和 MPS 6 酶的附加反应与 4 重反应分开进行。将两个反应淬灭并萃取，然后合并，然后进行单次 2 分钟 UPLC-MS/MS 分析。结果 2018年3月至2019年4月，通过8重LSD筛查试验对73,743名新生儿进行了筛查。 8 重测定显示出比之前的 4 重测定更好的分析精度，可能是因为 8 重测定是使用 UPLC-MS/MS 进行的。 6名新生儿被发现具有低MPS-4A酶（N-乙酰半乳糖胺-6-硫酸酯酶）活性和反式双等位基因GALNS致病性突变；这些患者可能受到 MPS4A 的影响，发病率为 12,291 分之一（95% 置信区间 (CI)：5633-26,817）。 GALNS 基因的一种突变，即 c.857C > T (p.T286 M)，占 12 个突变等位基因中的 5 个。这些新生儿在1月龄时椎体尚未成熟，其中1例从4月龄开始接受elosulfase alfa 2 mg/kg/周治疗。在其他筛查的 MPS 中，检出 MPS I 例 1 例、MPS II 例 3 例、MPS 3B 例 3 例。还诊断出 1 例 III 型粘脂沉积症。 与另外 9 名庞贝病、戈谢病和经典法布里病患者一起，LSD 的发病率为 3206 名新生儿中的 1 例（95% CI：2137 - 4811）。患有婴儿期庞贝氏病和戈谢病的婴儿分别从8天和41天开始接受治疗。结论 通过 8 重 LSD 筛查试验，可以对 MPS 4A 和其他 LSD 进行常规新生儿筛查。然而，详细的表型预测和开始治疗的时间需要进一步阐明。