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Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

Alessandro P Burlina1*, Katherine B Sims2, Juan M Politei3, Gary J Bennett4, Ralf Baron5, Claudia Sommer6, Anette Torvin Møller7 and Max J Hilz8

Author Affiliations

1 Neurological Unit, St. Bassiano Hospital, Bassano del Grappa, Italy

2 Center for Human Genetic Research and Neurology Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

3 Neuromuscular Disorders and Neuropathic Pain Section, Neurology Department, Juan A. Fernández Hospital, Buenos Aires, Argentina

4 Department of Anesthesia, Faculty of Dentistry, and the Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada

5 Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany

6 Department of Neurology, University of Würzburg, Würzburg, Germany

7 Department of Neurology, Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark

8 Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany, and Departments of Neurology, Medicine and Psychiatry, New York University, New York, USA

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BMC Neurology 2011, 11:61  doi:10.1186/1471-2377-11-61

Published: 27 May 2011



Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen.


An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain.


We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients.


Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate.

Diagnosis; Fabry Disease; Neuropathy; Pain; Treatment