Chronic pain affects more than 80% of late-onset Pompe disease patients
Study: Common measures of disease severity may not reflect pain burden
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More than 8 in 10 people with late-onset Pompe disease (LOPD) reported chronic nociceptive musculoskeletal pain, or pain affecting the muscles, bones, and surrounding tissues caused by damage or strain, a new study found.
However, pain was not associated with muscle weakness, walking ability, or structural changes in the muscles, suggesting that these commonly used measures of disease severity may not reflect the pain burden experienced by people with LOPD.
While 83% of participants with LOPD reported chronic pain, only about 3 in 10 reported pain on the day of their study visit. Researchers said this gap suggests that pain may be a distinct aspect of LOPD that is not fully captured by assessments made at a single point in time.
“Clinical management should focus on individualized pain assessment, as standard functional tests and snapshot pain assessments do not adequately reflect the patient’s pain burden,” researchers wrote.
The study, “Nociceptive pain in late-onset Pompe disease: prevalence, distribution, and clinical correlates,” was published in the Journal of Neurology.
Pain can persist despite treatment
Pompe disease is caused by genetic mutations that result in the buildup of glycogen, a complex sugar, to toxic levels inside cells, particularly muscle cells. This leads to symptoms such as progressive muscle weakness, poor muscle tone, and fatigue. In LOPD, symptoms can emerge at any time from childhood through adulthood.
Musculoskeletal pain is increasingly recognized as an important but underreported symptom of LOPD. It can emerge early and become more common as the disease progresses, substantially affecting quality of life. Pain may also persist or worsen despite enzyme replacement therapy, the standard treatment for Pompe disease, indicating that the mechanisms driving pain are poorly understood.
“In particular, it remains unclear whether pain in LOPD is directly related to measurable disease severity, such as muscle weakness or structural muscle alterations, or whether additional factors, including potential modulators, contribute to its manifestation,” the researchers wrote.
Pain in LOPD may fluctuate over time
To investigate, a team of researchers in Germany enrolled 103 adults between May 2022 and October 2024. Of these, 42 had genetically confirmed LOPD and 61 had other slowly progressing neuromuscular diseases, 20 with inclusion body myositis (IBM), 21 with facioscapulohumeral muscular dystrophy (FSHD), and 20 with spinal muscular atrophy type 3 (SMA3).
The four groups generally had similar walking ability and levels of fatigue. Although overall muscle strength differed across the groups, further comparisons between individual groups did not identify significant differences.
The team assessed chronic pain using questionnaires and body diagrams on which participants marked where they experienced pain. Researchers also measured muscle strength and used ultrasound to look for structural changes in the muscles. Blood markers and genetic factors that could potentially influence muscle function or pain were also analyzed.
Chronic nociceptive musculoskeletal pain was reported by 83.3% of people with LOPD, a significantly higher proportion than among people with IBM (40%), FSHD (57.1%), or SMA3 (55%). Pain affected mainly the upper legs and muscles along the trunk, broadly reflecting the areas commonly affected by muscle weakness in LOPD.
Yet the picture was very different when participants were asked whether they were experiencing pain on the day of the study visit. Only 30.9% of people with LOPD reported pain that day, significantly fewer than the 83.3% who reported chronic pain. A similar significant gap was seen in people with SMA3.
These findings support the concept of pain as a distinct clinical domain requiring dedicated assessment and management.
According to the researchers, this discrepancy suggests that pain in LOPD may fluctuate over time and possibly with activity, meaning that assessing pain at a single clinic visit may not capture its full burden.
The team next looked for factors that might explain why some people experienced chronic pain. However, pain was not significantly associated with muscle strength or walking ability. It also did not align with structural muscle changes seen on ultrasound, suggesting that people with more extensive muscle damage did not necessarily experience more pain.
Likewise, pain was not associated with age, disease duration, body mass index (a measure of body fat based on height and weight), or blood levels of creatine kinase, a marker of muscle damage, or vitamin D, the deficiency of which has been linked to muscle pain and increased pain sensitivity.
Two common genetic variants in the ACE and ACTN3 genes, which have been proposed as modifiers of muscle characteristics and disease severity in neuromuscular disorders, were also not associated with chronic pain.
“Musculoskeletal pain is a frequent but largely independent clinical feature in LOPD that is not explained by muscle strength, structural damage, biochemical parameters, or common genetic modifiers,” the researchers concluded. “These findings support the concept of pain as a distinct clinical domain requiring dedicated assessment and management.”
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