Small fibre neuropathy in Fabry disease

Abstract

Fabry disease is an X-linked inherited lysosomal storage disorder associated with glycosphingolipid accumulation in organs and vascular endothelium [1]. Neuropathic pain is common in Fabry disease and is associated with small fibre neuropathy [2, 3]. The diagnosis of small fibre neuropathy is based on symptoms like paresthesias, dysesthesias and pain and clinical signs with abnormal pin prick sensation, quantitative sensory testing (QST) and skin biopsy [4]. Corneal confocal microscopy examination of patients with diabetes mellitus as well as Fabry disease has demonstrated a reduction in sub-basal nerve density, also reflecting small fibre neuropathy [5–7]. In the present study we have compared these tests in patients with Fabry disease. Fifteen patients (five males with mean age of 16.2 years and 10 females with mean age of 33.8 years) with Fabry disease, all verified by mutation analysis, were recruited from the Bergen Fabry cohort at Haukeland University Hospital, Bergen, Norway (2004–2009). Blood levels of alpha-galactosidase varied from 2.2 to 37.8 lkat/kg protein (N: 17.7–26.4). All patients had episodes of neuropathic pain aggravated by heat. Eleven sexand age-matched healthy individuals served as controls for the assessment of small fibre affection. The disease severity scoring system (DS3) was used to measure the general neurological, cardiovascular and renal symptoms and signs in the Fabry patients [8]. Age was positively correlated with the DS3 total score (r = 0.68, p = 0.005; Pearson’s test), while it was negatively associated with the DS3 peripheral nervous system (PNS) score (r = -0.52, p = 0.045; Pearson’s test). Males had higher DS3 PNS score than females (p = 0.043; t test), but there was no sex association with DS3 total score (p = 0.73; t test). The alpha-galactosidase levels were not associated with the DS3 PNS score (r = 0.40, p = 0.135; Pearson’s test). Routine clinical and neurological examination, nerve conduction studies, electromyography, and QST (vibrametry and thermotests) were performed. A slit scanning confocal microscope (Confoscan 3, Nidek Technologies, Vigonza, Italy) was used to measure the sub-basal cornea nerve fibre length (CNFL) (mm/mm) in the central cornea of one eye of each subject. Skin-punch biopsy from the A. K. Bertelsen J. Aarseth C. A. Vedeler (&) Department of Neurology, Haukeland University Hospital, Bergen, Norway e-mail: christian.vedeler@helse-bergen.no