Muscle pathology is an accurate method to diagnose Pompe disease (PD) that resulted in no false negatives in a study recently published in the Journal of Neurology, Neurosurgery & Psychiatry

Previous publications have reported that PD is less prevalent in Japan than in neighboring countries, raising the possibility of overlooked patients. Therefore, a research institution screened for PD in all muscle biopsy samples received between July 2015 and January 2018 to find the reliability of the disease prevalence.

To conduct this study, acid α-glucosidase (GAA) activity was assayed in a prospective cohort using 10-µm frozen muscle sections from 2408 biopsies, performing genetic analyses on samples with decreased activity. Additionally, a retrospective analysis assessed the number of myopathologically diagnosed patients from 1978 to 2020.

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Regarding the retrospective cohort, 41 patients from Japan were histopathologically diagnosed with PD between 1978 and 2020. The average number of individuals with PD was 5 in 5 years from 1981 to 2020. The number decreased in a stepwise fashion, which was most likely attributable to increased awareness due to a clinical trial conducted in the United States in 2001.

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By 2010, there were no diagnoses of the infantile form by biopsy, while the juvenile form decreased by 50%. There were no new histopathological diagnoses by 2020. However, the prospective analysis found that the number of individuals with low enzymatic activity levels was significantly greater in patients with the AA/AA diplotype than in those with other diplotypes. 

“Although no muscle biopsy samples were pathologically diagnosed with PD in this study, screening using muscle sections revealed low GAA activity in 163 samples,” the authors said. “However, no samples had biallelic pathogenic variants in the GAA gene, suggesting that the routine muscle pathology diagnosis resulted in no false-negative results in this study.”

PD is an autosomal recessive disease caused by mutations in the GAA gene. Glycogen accumulation and tissue damage vary based on residual enzyme activity. GAA activity is nearly 0 in patients with the infantile form of PD, characterized by hypotonia and hypertrophic cardiomyopathy within a few months after birth. The adult form may present with nonspecific characteristics, such as a limb-girdle phenotype without cardiomyopathy. A prompt diagnosis of PD allows for timely enzyme replacement therapy, a more favorable prognosis, and better quality of life.


Saito Y, Nakamura K, Fukuda T, et al. Muscle biochemical and pathological diagnosis in Pompe disease. J Neurol Neurosurg Psychiatry. Published online April 25, 2022. doi:10.1136/jnnp-2022-329085