Idiopathic small fiber neuropathy: phenotype, etiologies, and the search for fabry disease.
OBJECTIVE
The etiology of small fiber neuropathy (SFN) often remains unclear. Since SFN may be the only symptom of late-onset Fabry disease, it may be underdiagnosed in patients with idiopathic polyneuropathy. We aimed to uncover the etiological causes of seemingly idiopathic SFN by applying a focused investigatory procedure, to describe the clinical phenotype of true idiopathic SFN, and to elucidate the possible prevalence of late-onset Fabry disease in these patients.


METHODS
Forty-seven adults younger than 60 years with seemingly idiopathic pure or predominantly small fiber sensory neuropathy underwent a standardized focused etiological and clinical investigation. The patients deemed to have true idiopathic SFN underwent genetic analysis of the alpha-galactosidase A gene (GLA) that encodes the enzyme alpha-galactosidase A (Fabry disease).


RESULTS
The following etiologies were identified in 12 patients: impaired glucose tolerance (58.3%), diabetes mellitus (16.6%), alcohol abuse (8.3%), mitochondrial disease (8.3%), and hereditary neuropathy (8.3%). Genetic alterations of unknown clinical significance in GLA were detected in 6 of the 29 patients with true idiopathic SFN, but this rate did not differ significantly from that in healthy controls (n=203). None of the patients with genetic alterations in GLA had significant biochemical abnormalities simultaneously in blood, urine, and skin tissue.


CONCLUSIONS
A focused investigation may aid in uncovering further etiological factors in patients with seemingly idiopathic SFN, such as impaired glucose tolerance. However, idiopathic SFN in young to middle-aged Swedish patients does not seem to be due to late-onset Fabry disease.
Department of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Kristin
K
Samuelsson
Department of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Konstantinos
K
Kostulas
Division of Neurology and Clinical Neurophysiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Magnus
M
Vrethem
Albrecht-Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany.
Arndt
A
Rolfs
Department of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Rayomand
R
Press
Fabry disease; etiology; idiopathic; impaired glucose tolerance; small fiber neuropathy