Wencel Marie, Shaibani Aziz, Goyal Namita A, Dimachkie Mazen M, Trivedi Jaya, Johnson Nicholas E, Gutmann Laurie, Wicklund Matthew P, Bandyopadhay Sankar, Genge Angela L, Freimer Miriam L, Goyal Neelam, Pestronk Alan, Florence Julaine, Karam Chafic, Ralph Jeffrey W, Rasheed Zinah, Hays Melissa, Hopkins Steve, Mozaffar Tahseen
Department of Neurology (M.W., N.A.G., T.M.), University of California, Irvine; Nerve and Muscle Center of Texas (A.S., Z.R.), Houston, TX; Department of Neurology (M.M.D., M.H.), University of Kansas Medical Center; Department of Neurology and Neurotherapeutics (J.T., S.H.), University of Texas Southwestern, Dallas; Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond (affiliated with University of Utah, Salt Lake City at the Time of Study); Department of Neurology (L.G.), Indiana University School of Medicine, Indianapolis (affiliated with University of Iowa at the Time of Study); Department of Neurology (S.B.), Pennsylvania State University, Hershey; Department of Neurology (M.P.W.), UC Denver, CO (affiliated with Department of Neurology, Pennsylvania State University, Hershey at the Time of the Study); Department of Neurology and the Montreal Neurological Institute (A.L.G.), McGill University, Montreal, Quebec, Canada; Department of Neurology (M.L.F.), Ohio State University, Columbus; Department of Neurology (N.G.), Stanford University, Palo Alto, CA; Department of Neurology and Pathology (A.P., J.F.), Washington University, St. Louis, Missouri; Department of Neurology (A.P., C.K.), University of Pennsylvania, Philadelphia (affiliated with Oregon Health & Science University, Portland at the Time of Study); Department of Neurology (J.W.R.), University of California, San Francisco; and Departments of Neurology (T.M.), Orthopaedic Surgery and Pathology and Laboratory Medicine, University of California, Irvine.
Neurol Genet. 2021 Oct 18;7(6):e623. doi: 10.1212/NXG.0000000000000623. eCollection 2021 Dec.
We investigated the prevalence of late-onset Pompe disease (LOPD) in patients presenting to 13 academic, tertiary neuromuscular practices in the United States and Canada.
All successive patients presenting with proximal muscle weakness or isolated hyperCKemia and/or neck muscle weakness to these 13 centers were invited to participate in the study. Whole blood was tested for acid alpha-glucosidase (GAA) assay through the fluorometric method, and all cases with enzyme levels of ≤10 pmoL/punch/h were reflexed to molecular testing for mutations in the GAA gene. Clinical and demographic information was abstracted from their clinical visit and, along with study data, entered into a purpose-built REDCap database, and analyzed at the University of California, Irvine.
GAA enzyme assay results were available on 906 of the 921 participants who consented for the study. LOPD was confirmed in 9 participants (1% prevalence). Another 9 (1%) were determined to have pseudodeficiency of GAA, whereas 19 (1.9%) were found to be heterozygous for a pathogenic GAA mutation (carriers). Of the definite LOPD participants, 8 (89%) were Caucasian and were heterozygous for the common leaky (IVS1) splice site mutation in the GAA gene (c -32-13T>G), with a second mutation that was previously confirmed to be pathogenic.
The prevalence of LOPD in undiagnosed patients meeting the criteria of proximal muscle weakness, high creatine kinase, and/or neck weakness in academic, tertiary neuromuscular practices in the United States and Canada is estimated to be 1%, with an equal prevalence rate of pseudodeficiency alleles.
Clinical trial registration number: NCT02838368.
我们调查了美国和加拿大13家学术性三级神经肌肉诊疗机构中迟发型庞贝病（LOPD）的患病率。
所有因近端肌无力或孤立性高肌酸激酶血症和/或颈部肌无力而到这13个中心就诊的连续患者均受邀参加本研究。通过荧光法检测全血中的酸性α-葡萄糖苷酶（GAA）活性，所有酶水平≤10 pmoL/打孔/小时的病例均进行GAA基因突变的分子检测。从患者临床就诊记录中提取临床和人口统计学信息，并与研究数据一起录入专门构建的REDCap数据库，由加利福尼亚大学欧文分校进行分析。
921名同意参加研究的参与者中，906人的GAA酶活性检测结果可用。9名参与者（患病率1%）确诊为LOPD。另有9名（1%）被确定为GAA假性缺陷，而19名（1.9%）被发现为致病性GAA基因突变的杂合子（携带者）。在确诊的LOPD参与者中，8名（89%）为白种人，是GAA基因常见的渗漏（IVS1）剪接位点突变（c -32-13T>G）的杂合子，且有另一个先前已证实为致病性的突变。
在美国和加拿大的学术性三级神经肌肉诊疗机构中，符合近端肌无力、高肌酸激酶和/或颈部肌无力标准的未确诊患者中，LOPD的患病率估计为1%，假性缺陷等位基因的患病率与之相当。
临床试验注册号：NCT02838368。
