Researchers determined that pain may be independent of the number of small nerve fibers in patients with Pompe disease (PD), as published in the Orphanet Journal of Rare Diseases.

Enax-Krumova and the team included 35 patients previously diagnosed with late-onset PD who were receiving enzyme replacement therapy (ERT), and 20 healthy subjects in the control group. Skin samples to study intraepidermal nerve fiber density (IENFD) were collected from all participants.

Patients with PD completed the PainDETECT Questionnaire (PD-Q) and the Hospital Anxiety Depression Scale (HADS) to assess polyneuropathy and depressive and/or anxiety symptoms.

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Over half (69%) of the patients in the PD group presented with pain, with an average intensity of 4.1±1.1 on a scale from 0 to 10. According to the PD-Q, only 1 patient likely had neuropathic pain. After analyzing the HADS, depression and anxiety symptoms were present in 31% and 23% of the cases, respectively. As expected, these symptoms correlated with pain intensity.

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Moreover, the biopsies reported that 57% of the patients with PD had lower IENFD when compared to the control group, but this reduction did not correlate with either the duration of symptoms up to the beginning of the ERT or the duration of the treatment prior to the biopsy.

“The reduction of small dermal nerve fibers as shown in our study, might result from pathological glycogen storage and cell dysfunction in the peripheral nervous system e.g. Schwann cells or dorsal root ganglion cells,” the authors said. “Glycogen deposits were also found in smooth muscle vascular cells and might be associated with cutaneous microcirculation dysfunction.”

The decreased small nerve fiber density in the PD group suggests the pathophysiology of this entity affects the peripheral nervous system; nonetheless, this anatomical finding may not be responsible for the neuropathic pain characteristic in these patients.

“Future studies including standardized longitudinal assessments of [late-onset PD] regarding small nerve fiber pathology and function, as recently presented for [small fiber neuropathy] may give further information both on the underlying mechanisms of small nerve fiber degeneration and pain generation and on the disease’s progress, thus potentially contributing to personalized treatment,” the authors concluded.


Enax-Krumova E, Dahlhaus I, Görlach J, et al. Small fiber involvement is independent from clinical pain in late-onset Pompe disease. Orphanet J Rare Dis. Published online April 27, 2022. doi:10.1186/s13023-022-02327-4