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Short report
Muscle biochemical and pathological diagnosis in Pompe disease
  1. Yoshihiko Saito1,
  2. Kimitoshi Nakamura2,
  3. Tokiko Fukuda3,
  4. Hideo Sugie4,
  5. Shinichiro Hayashi1,
  6. Satoru Noguchi1,
  7. Ichizo Nishino1
  1. 1Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan
  2. 2Department of Pediatrics, Kumamoto University, Kumamoto, Japan
  3. 3Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan
  4. 4Faculty of Health and Medical Sciences, Tokoha University, Hamamatsu, Japan
  1. Correspondence to Dr Ichizo Nishino, Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Tokyo, Japan; nishino{at}


Background and objectives Pompe disease is reportedly less prevalent in Japan than in neighbouring countries, raising a possibility that some patients may be overlooked. Therefore, all muscle biopsy samples received at our institute were screened for Pompe disease to determine the accuracy of the disease prevalence.

Methods The acid α-glucosidase (GAA) activity was assayed using 10 µm frozen muscle sections from 2408 muscle biopsies received between July 2015 and January 2018. Genetic analysis was performed for samples with decreased activity. The number of myopathologically diagnosed patients was retrospectively assessed.

Results The GAA activity was distributed similarly to previous results from dried blood spot screening. GAA activity measured using muscle sections corresponded to that measured using muscle blocks. Of 163 patients with GAA activity <3 nmol/hour/mg protein, 43 (26%) patients had homozygous pseudodeficiency alleles in GAA (p.G576S and p.E689K). In the retrospective analysis, the number of patients diagnosed with Pompe disease via muscle biopsies decreased to zero over time.

Discussion Muscle pathology is an accurate method to diagnose Pompe disease. It is unlikely that a significant number of patients with Pompe disease are overlooked. Pathological variants were rare, and the majority carried a pseudodeficiency allele, which further supports our conclusion.


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  • Contributors YS and IN had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design—YS and IN. Acquisition, analysis or interpretation of data—YS, SH, SN and IN. Drafting of the manuscript—YS, SH, SN and IN. Critical revision of the manuscript for important intellectual content—all authors. Statistical analysis—YS and SN. Obtained funding—IN. Administrative, technical or material support—YS, SH, SN and IN. Supervision—IN.

  • Funding This study was funded by the NCNP (Intramural Research Grant: 2-5 and 29-4 for Neurological and Psychiatric Disorders) to IN under grant number JP19ek0109285h0003. This study was supported in part by JSPS KAKENHI (grant numbers JP16K09728, JP 17K09785, JP 18K07082); Intramural Research Grant (29–4, 29–3, 28–6, 30–9) for Neurological and Psychiatric Disorders of NCNP; AMED under grant numbers JP18ek0109285h0002, JP18dk0310072h0003, JP18ek010934h0001, JP18kk0205001s0203, JP18ek0109348s0501; and Health, Labour and Welfare Sciences Research Grants (H28–Nanchito(Nan)–Ippan–030, H29–Nanchito(Nan)–Ippan–030).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.