Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study

Abstract

BackgroundFabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).MethodsIn this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.ResultsAll Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.ConclusionSmall fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.

In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

“…However, with the finding that abnormalities were also found in the patients without FD (specificity 80%), it is safe to draw the conclusion that small nerve fibre assessment is most likely an unsuitable tool for establishing the diagnosis of FD in patients who present with an uncertain diagnosis. In previous studies, it has been shown that all male and most female patients with (mostly classical) FD have small nerve fibre pathology, as assessed with QST alone or in combination with an IENFD assessment (Dutsch et al 2002;Laaksonen et al 2008;Biegstraaten et al 2011Biegstraaten et al , 2012€ Uçeyler et al 2011€ Uçeyler et al , 2013. With this study, we confirmed our hypothesis that in patients with the nonclassical phenotype QST and/or IENFD may be abnormal, even in the absence of pain.…”

“…Previous studies have shown that all male and most female patients with (classical) FD have an abnormal quantitative sensory testing (QST) profile and a decreased intraepidermal nerve fibre density (IENFD) in a skin biopsy at the distal leg (Dutsch et al 2002;Laaksonen et al 2008;Biegstraaten et al 2011Biegstraaten et al , 2012€ Uçeyler et al 2011€ Uçeyler et al , 2013. We hypothesized that QST and IENFD could aid in the diagnosis of FD in patients who initially present with an uncertain diagnosis.…”

Cold‐evoked potentials versus contact heat‐evoked potentials—Methodological considerations and clinical application

“…The assessment of cold perception is thought to be an important somatosensory entity, which may be altered in the early stage of small‐fibre neuropathy (such as in Fabry's disease; (Maag et al, ; Uceyler et al, )). Previous studies reported cold sensation loss in 40% of polyneuropathy, 63% of postherpetic neuralgia, 50% of peripheral nerve injury and 49% of central pain patients (Maier et al, ).…”

Small-fibre neuropathies and skin: news and perspectives for dermatologists

“…The pathophysiology of pain in Fabry disease is not fully understood; however, SFN as a result of glycolipid accumulation in the dorsal root ganglia has been proposed [39] and confirmed [40] as a mechanism. Indeed, small fibre conduction is impaired in men with Fabry disease and worsens with advanced disease severity [41]. Indeed, 100% of male patients and 57% of female patients have a decrease of IENF density [40].…”