From the Center for Lysosomal and Metabolic Diseases (M.J.M., J.J.A.v.d.D., A.T.v.d.P., J.M.P.v.d.H.), Department of Paediatrics, Erasmus University Medical Center, Rotterdam; Neurochemistry laboratory (E.A.J.W., C.T.), Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centres, VU University, the Netherlands; Departments of Biomedizin and Neurology (E.A.J.W.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital Basel and University of Basel, Switzerland; Center for Lysosomal and Metabolic Diseases (N.A.M.E.v.d.B.), Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands; John Walton Muscular Dystrophy Research Centre (J.D.-M.), Newcastle University, United Kingdom; Neuromuscular Disorders Laboratory (J.D.-M.), Institut de recerca de l'hospital de la Santa Creu I Sant Pau, Barcelona; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (J.D.-M.), Madrid, Spain; and Department of Biostatistics & Department of Epidemiology (D.R.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Neurology. 2023 Aug 8;101(6):e594-e601. doi: 10.1212/WNL.0000000000207482. Epub 2023 Jun 19.
Enzyme replacement therapy (ERT) has substantially improved the outcome of classic infantile Pompe disease, an inheritable muscle disease previously fatal at infancy. However, under treatment, patients develop white matter abnormalities and neurocognitive problems. Therefore, upcoming therapies also target the brain. Currently, biomarkers reflecting CNS involvement are lacking. We aimed to study the association of neurofilament light (NfL) and CNS involvement.
To investigate the potential of NfL, we analyzed serum samples of patients with classic infantile Pompe disease who were treated with ERT. The samples were collected at ages of <1, 5, and 10 years, as well as around MRI scans. We compared the outcomes with levels in age- and sex-matched peers. Control samples were originally collected as part of routine blood work in children who underwent small surgeries and stored in the biobank of the Erasmus MC/Sophia Children's Hospital.
We analyzed 74 serum samples of 17 patients collected at ages ranging from 22 days to 21.2 years (1-8 samples per patient) and compared these with outcomes of 71 matched peers. In the first year of age, NfL levels in patients and controls were similar (10.3 vs 11.0 pg/mL), but mixed linear model analysis showed a yearly increase of NfL of 6.0% in patients, compared with a decrease of 8.8% in controls ( < 0.001). Higher NfL was associated with lower IQ scores ( = 0.009) and lower processing speed scores ( = 0.001).
We found significant differences in NfL levels between patients and controls and a good association between NfL and cognition. NfL deserves further exploration as a biomarker for CNS involvement in patients with classic infantile Pompe disease.
酶替代疗法（ERT）显著改善了经典婴儿型庞贝病（一种以前在婴儿期致命的遗传性肌肉疾病）的预后。然而，在治疗过程中，患者会出现白质异常和神经认知问题。因此，即将出现的治疗方法也针对大脑。目前，缺乏反映中枢神经系统受累的生物标志物。我们旨在研究神经丝轻链（NfL）与中枢神经系统受累的关系。
为了研究 NfL 的潜力，我们分析了接受 ERT 治疗的经典婴儿型庞贝病患者的血清样本。这些样本采集于患者年龄<1 岁、5 岁和 10 岁时，以及 MRI 扫描前后。我们将结果与年龄和性别匹配的同龄人的水平进行了比较。对照样本最初是作为在 Erasmus MC/Sophia 儿童医院接受小手术的儿童常规血液检查的一部分收集的，并储存在生物库中。
我们分析了 17 名患者的 74 份血清样本，采集年龄从 22 天到 21.2 岁不等（每个患者 1-8 个样本），并将这些结果与 71 名匹配的同龄人进行了比较。在 1 岁时，患者和对照组的 NfL 水平相似（10.3 与 11.0 pg/mL），但混合线性模型分析显示，与对照组相比，患者的 NfL 每年增加 6.0%，而对照组下降 8.8%（<0.001）。较高的 NfL 与较低的智商得分（=0.009）和较低的处理速度得分（=0.001）相关。
我们发现患者和对照组之间的 NfL 水平存在显著差异，并且 NfL 与认知能力之间存在良好的相关性。NfL 值得进一步探索作为经典婴儿型庞贝病患者中枢神经系统受累的生物标志物。
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