Differentiation between late-onset Pompe disease (PD) and inflammatory myositis may pose a diagnostic challenge in which a correct muscle biopsy interpretation could be crucial, according to a recently published case report in the European Journal of Rheumatology.
Unlike the rapidly progressive infantile-onset form, late-onset PD often represents a clinical challenge, mainly due to its relatively milder presentation and later symptom onset. Furthermore, common features such as elevated muscle enzymes, dyspnea with exertion, and muscle weakness, among others, make a differential diagnosis with inflammatory myositis a must.
The case involved a 30-year-old woman with a 2-year history of proximal muscle weakness and fatigue. The patient was initially diagnosed with polymyositis on the basis of suggestive electromyography (EMG) findings, elevated muscle enzymes, and a muscle biopsy that reported mild lymphocytic infiltration. Due to poor response to treatment with corticosteroids, methotrexate, and azathioprine, the patient was referred for a second opinion.
“Patients who are negative for [connective tissue disease]-related findings and resistant to [immunosuppressive] therapies should lead to suspicion of adult-onset Pompe disease,” the authors wrote.
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Physical examination revealed decreased muscle strength in the proximal lower extremities with a positive Gowers sign; the rest of the physical exam was unremarkable. As expected, muscle enzymes were elevated and a repeated EMG showed positive sharp waves consistent with myopathy. However, antinuclear antibodies and myositis-specific antibodies were negative. Magnetic resonance imaging revealed muscle edema and fatty atrophic changes.
In light of the findings, the attending physicians performed a second muscle biopsy, which showed cytoplasmic vacuolization consistent with vacuolar myopathy and suggestive of metabolic myopathy. Although no glycogen deposition was found, Oil Red O staining revealed lipid droplets.
A low acid alpha-glucosidase enzyme level led to targeted genetic sequencing, which confirmed the late-onset PD diagnosis. After the initiation of enzyme replacement therapy, the patient showed significant improvement.
“In conclusion, [late-onset PD] and inflammatory myopathies share similar clinical and laboratory findings, and it could be hard to differentiate,” the authors concluded.
Yüce İnel T, Köken Avşar A, Teke Kısa P, Özer E, Sarı İ. A challenging etiology of myopathy: the late-onset Pompe disease. Eur J Rheumatol. Published online April 6, 2022. doi:10.5152/eurjrheum.2022.21156