RT Journal Article
SR Electronic
T1 Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e623
DO 10.1212/NXG.0000000000000623
VO 7
IS 6
A1 Wencel, Marie
A1 Shaibani, Aziz
A1 Goyal, Namita A.
A1 Dimachkie, Mazen M.
A1 Trivedi, Jaya
A1 Johnson, Nicholas E.
A1 Gutmann, Laurie
A1 Wicklund, Matthew P.
A1 Bandyopadhay, Sankar
A1 Genge, Angela L.
A1 Freimer, Miriam L.
A1 Goyal, Neelam
A1 Pestronk, Alan
A1 Florence, Julaine
A1 Karam, Chafic
A1 Ralph, Jeffrey W.
A1 Rasheed, Zinah
A1 Hays, Melissa
A1 Hopkins, Steve
A1 Mozaffar, Tahseen
A1 ,
YR 2021
UL http://ng.neurology.org/content/7/6/e623.abstract
AB Background and Objectives 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.Methods 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.Results 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.Discussion 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.Trial Registration Information Clinical trial registration number: NCT02838368.CK=creatine kinase; DBS=dried blood spotted; GAA=acid alpha-glucosidase; LGMD=limb girdle muscular dystrophy; LOPD=late-onset Pompe disease; MDA=muscular dystrophy association; NBS=newborn screening program