Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 18;7(6):e623.
doi: 10.1212/NXG.0000000000000623. eCollection 2021 Dec.

Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study

Marie Wencel  1 , Aziz Shaibani  1 , Namita A Goyal  1 , Mazen M Dimachkie  1 , Jaya Trivedi  1 , Nicholas E Johnson  1 , Laurie Gutmann  1 , Matthew P Wicklund  1 , Sankar Bandyopadhay  1 , Angela L Genge  1 , Miriam L Freimer  1 , Neelam Goyal  1 , Alan Pestronk  1 , Julaine Florence  1 , Chafic Karam  1 , Jeffrey W Ralph  1 , Zinah Rasheed  1 , Melissa Hays  1 , Steve Hopkins  1 , Tahseen Mozaffar  1
Affiliations

Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study

Marie Wencel et al. Neurol Genet. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. CONSORT Diagram for the Study
Figure 2
Figure 2. CK Values
There is no correlation between serum creatine kinase (CK) and acid alpha-glucosidase (GAA) levels. On Pearson correlation testing, there was no correlation between the CK levels and the GAA levels (r = 0.06; p = 0.09) in the overall population. Inset: Serum CK distribution in all 766 subjects (340 women and 424 men, 2 sex unspecified). Mean CK for all subjects was 1,472 (3,649) IU/L. Mean CK value for male subjects was 1332.3 (3,328) IU/L, whereas in women, the mean CK value was 801.9 (2,437) IU/L. The difference between CK values in men and women was significant (p = 0.01).
See this image and copyright information in PMC

References

    1. Hagemans ML, Winkel LP, Doorn VPA, et al. . Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain. 2005;128(pt 3):671-677. - PubMed
    1. Lim J-AA, Kakhlon O, Li L, Myerowitz R, Raben N. Pompe disease: shared and unshared features of lysosomal storage disorders. Rare Dis. 2015;3(1):e1068978. - PMC - PubMed
    1. American Association of Neuromuscular and Electrodiagnostic Medicine. Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle Nerve. 2009;40(1):149-160. - PubMed
    1. van der Ploeg AT, Clemens PR, Corzo D, et al. . A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Engl J Med. 2010;362(15):1396-1406. - PubMed
    1. Ausems MG, Verbiest J, Hermans MP, et al. . Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet. 1999;7(6):713-716. - PubMed

Associated data