Frontiers in Neurology (Sep 2022)
High-risk screening of late-onset Pompe disease: A different early portrait in China
- Kexin Jiao,
- Kexin Jiao,
- Kexin Jiao,
- Jihong Dong,
- Sushan Luo,
- Sushan Luo,
- Sushan Luo,
- Liqiang Yu,
- Qing Ke,
- Zhiqiang Wang,
- Xinghua Luan,
- Xiaojie Zhang,
- Junhong Guo,
- Yan Chen,
- Xihua Li,
- Song Tan,
- Fangyuan Qian,
- Jianming Jiang,
- Xuen Yu,
- Dongyue Yue,
- Changxia Liu,
- Lijun Luo,
- Jianping Li,
- Yanzhou Qu,
- Lan Chen,
- Jianglong Tu,
- Chong Sun,
- Chong Sun,
- Chong Sun,
- Chong Yan,
- Chong Yan,
- Chong Yan,
- Jie Song,
- Jie Song,
- Jie Song,
- Jianying Xi,
- Jianying Xi,
- Jianying Xi,
- Jie Lin,
- Jie Lin,
- Jie Lin,
- Jiahong Lu,
- Jiahong Lu,
- Jiahong Lu,
- Chongbo Zhao,
- Chongbo Zhao,
- Chongbo Zhao,
- Wenhua Zhu,
- Wenhua Zhu,
- Wenhua Zhu,
- Qi Fang
Affiliations
- Kexin Jiao
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Kexin Jiao
- National Center for Neurological Disorders (NCND), Shanghai, China
- Kexin Jiao
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Jihong Dong
- Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China
- Sushan Luo
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Sushan Luo
- National Center for Neurological Disorders (NCND), Shanghai, China
- Sushan Luo
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Liqiang Yu
- Department of Neurology, The First Affiliated Hospital of Soochow University, Shanghai, China
- Qing Ke
- Department of Neurology, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China
- Zhiqiang Wang
- Department of Neurology, Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Xinghua Luan
- Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Xiaojie Zhang
- Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Junhong Guo
- Department of Neurology, First Hospital, Shanxi Medical University, Taiyuan, China
- Yan Chen
- 0Department of Neurology, Tongji Hospital, Tongji University, Shanghai, China
- Xihua Li
- 1Department of Neurology, Children's Hospital of Fudan University, Shanghai, China
- Song Tan
- 2Department of Neurology, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Fangyuan Qian
- 3Department of Neurology, School of Medicine, Affiliated ZhongDa Hospital, Research Institution of Neuropsychiatry, Southeast University, Nanjing, China
- Jianming Jiang
- 4Department of Neurology, First Affiliated Hospital to Naval Medical University, Shanghai, China
- Xuen Yu
- 5Affiliated Hospital of the Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China
- Dongyue Yue
- 6Department of Neurology, Jing'an District Center Hospital of Shanghai, Fudan University, Shanghai, China
- Changxia Liu
- 7Department of Neurology, The Fourth Affiliated Hospital of Nantong University, Yancheng, China
- Lijun Luo
- 8Department of Neurology, Wuhan No.1 Hospital, Wuhan, China
- Jianping Li
- 9Department of Geriatrics, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
- Yanzhou Qu
- 0Department of Neurology, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Lan Chen
- 1Department of Neurology, Nantong first people's Hospital, Nantong, Jiangsu, China
- Jianglong Tu
- 2Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Chong Sun
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Chong Sun
- National Center for Neurological Disorders (NCND), Shanghai, China
- Chong Sun
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Chong Yan
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Chong Yan
- National Center for Neurological Disorders (NCND), Shanghai, China
- Chong Yan
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Jie Song
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Jie Song
- National Center for Neurological Disorders (NCND), Shanghai, China
- Jie Song
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Jianying Xi
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Jianying Xi
- National Center for Neurological Disorders (NCND), Shanghai, China
- Jianying Xi
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Jie Lin
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Jie Lin
- National Center for Neurological Disorders (NCND), Shanghai, China
- Jie Lin
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Jiahong Lu
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Jiahong Lu
- National Center for Neurological Disorders (NCND), Shanghai, China
- Jiahong Lu
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Chongbo Zhao
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Chongbo Zhao
- National Center for Neurological Disorders (NCND), Shanghai, China
- Chongbo Zhao
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Wenhua Zhu
- Department of Neurology, Huashan Hospital Fudan University, Shanghai, China
- Wenhua Zhu
- National Center for Neurological Disorders (NCND), Shanghai, China
- Wenhua Zhu
- Huashan Rare Disease Center, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China
- Qi Fang
- Department of Neurology, The First Affiliated Hospital of Soochow University, Shanghai, China
- DOI
- https://doi.org/10.3389/fneur.2022.965207
- Journal volume & issue
-
Vol. 13
Abstract
IntroductionThe lack of knowledge regarding the differences between Chinese and other ethnicities in the early manifestation of late-onset Pompe disease (LOPD) prohibits the development of an effective screening strategy. We conducted a multicenter screening study to determine LOPD prevalence in high-risk populations and define the early manifestation of LOPD in China.MethodsBetween August 2020 and April 2021, the participants were prospectively identified through medical examination at 20 centers from inpatient departments and outpatient neuromuscular clinics in China. The inclusion criteria were as follows: (1) age ≥ 1 year and (2) either one of the following conditions: (a) persistent hyperCKemia, (b) muscle weakness of the axial and/or limb-girdle muscles, or (c) unexplained restrictive respiratory insufficiency (RI). Enzymatic activity of acid α-glucosidase (GAA) was measured in a dried blood spot (DBS) using a tandem mass spectrometry (MS/MS) assay. Next-generation sequencing (NGS) was used to evaluate all samples with decreased GAA activity, searching for GAA mutations and pseudodeficiency alleles.ResultsAmong the 492 cases, 26 positive samples (5.3%) were detected in the DBS test. Molecular studies confirmed a diagnosis of LOPD in eight cases (1.6%). Using MS/MS assay, GAA activities in individuals with pseudodeficiency could be distinguished from those in patients with LOPD. The median interval from the onset of symptoms to diagnosis was 5 years. All patients also showed RI, with a mean forced vital capacity (FVC) of 48%, in addition to axial/proximal muscle weakness. The creatine kinase (CK) level ranged from normal to no more than 5-fold the upper normal limit (UNL). LOPD with isolated hyperCKemia was not identified.ConclusionLess frequent hyperCKemia and predominant RI depict a different early portrait of adult Chinese patients with LOPD. A modified high-risk screening strategy should be proposed for the early diagnosis of Chinese patients with LOPD.
Keywords
- late-onset Pompe disease
- respiratory failure
- high-risk screening
- tandem mass spectrometry
- dried blood spot
