关键词： Acid α-glucosidase CLIR, Collaborative Laboratory Integrated Reports CRIM, cross-reactive immunological material DBS, dried blood spot DMF, digital microfluidics ECG, electrocardiogram EF, ejection fraction EMG, electromyography ERT, enzyme replacement therapy Enzyme replacement therapy GAA, acid α-glucosidase GMFM-88, Gross Motor Function Measure Glc4, glucose tetrasaccharide IOPD, infantile-onset Pompe disease ITI, immunotolerance induction LOPD, late-onset Pompe disease LVMI, left ventricular max index MFM-20, motor function measurement MRC, Medical Research Council Scale MRI, magnetic resonance imaging MS/MS, tandem mass spectrometry NBS, newborn screening Newborn screening PBMC, peripheral blood mononuclear cells PD, Pompe disease PPV, positive predictive value Pompe disease RUSP, Recommended Uniform Screening Panel Tandem mass-spectrometry Urinary tetrasaccharide VUS, variants of uncertain significance. nv, normal values rhGAA, recombinant human GAA

来  源：   DOI：10.1016/j.ymgmr.2022.100929   PDF(Pubmed)

Abstract：
Pompe disease (PD) is a progressive neuromuscular disorder caused by a lysosomal acid α-glucosidase (GAA) deficiency. Enzymatic replacement therapy is available, but early diagnosis by newborn screening (NBS) is essential for early treatment and better outcomes, especially with more severe forms. We present results from 7 years of NBS for PD and the management of infantile-onset (IOPD) and late-onset (LOPD) patients, during which we sought candidate predictive parameters of phenotype severity at baseline and during follow-up. We used a tandem mass spectrometry assay for α-glucosidase activity to screen 206,741 newborns and identified 39 positive neonates (0.019%). Eleven had two pathogenic variants of the GAA gene (3 IOPD, 8 LOPD); six carried variants of uncertain significance (VUS). IOPD patients were treated promptly and had good outcomes. LOPD and infants with VUS were followed; all were asymptomatic at the last visit (mean age 3.4 years, range 0.5-5.5). Urinary glucose tetrasaccharide was a useful and biomarker for rapidly differentiating IOPD from LOPD and monitoring response to therapy during follow-up. Our study, the largest reported to date in Europe, presents data from longstanding NBS for PD, revealing an incidence in North East Italy of 1/18,795 (IOPD 1/68,914; LOPD 1/25,843), and the absence of mortality in IOPD treated from birth. In LOPD, rigorous long-term follow-up is needed to evaluate the best time to start therapy. The high pseudodeficiency frequency, ethical issues with early LOPD diagnosis, and difficulty predicting phenotypes based on biochemical parameters and genotypes, especially in LOPD, need further study.
摘要：
庞贝氏病（PD）是由溶酶体酸性α-葡萄糖苷酶（GAA）缺乏引起的进行性神经肌肉疾病。有酶替代疗法,但是通过新生儿筛查（NBS）进行早期诊断对于早期治疗和更好的结局至关重要，尤其是更严重的形式。我们介绍了7年的PDNBS以及婴儿发作（IOPD）和晚发性（LOPD）患者的管理结果，在此期间,我们在基线和随访期间寻找表型严重程度的候选预测参数.我们使用串联质谱测定α-葡萄糖苷酶活性来筛选206,741例新生儿，并鉴定出39例阳性新生儿（0.019％）。11具有GAA基因的两种致病变体（3IOPD，8LOPD）；六个携带的不确定意义的变体（VUS）。IOPD患者得到及时治疗，预后良好。随访LOPD和有VUS的婴儿；在最后一次就诊时全部无症状（平均年龄3.4岁，范围0.5-5.5）。尿葡萄糖四糖是快速区分IOPD和LOPD并在随访期间监测对治疗的反应的有用生物标志物。我们的研究,迄今为止欧洲最大的报道，提供了来自长期国家统计局的PD数据，显示意大利东北部的发病率为1/18,795（IOPD1/68,914；LOPD1/25,843），以及从出生开始治疗的IOPD中没有死亡率。在LOPD中,需要严格的长期随访以评估开始治疗的最佳时间.假性缺乏症的频率很高，早期LOPD诊断的伦理问题，以及根据生化参数和基因型预测表型的困难，尤其是在LOPD中，需要进一步研究。
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