No Fabry Disease in Patients Presenting with Isolated Small Fiber Neuropathy - PubMed (original) (raw)

No Fabry Disease in Patients Presenting with Isolated Small Fiber Neuropathy

Bianca T A de Greef et al. PLoS One. 2016.

Abstract

Objective: Screening for Fabry disease in patients with small fiber neuropathy has been suggested, especially since Fabry disease is potentially treatable. However, the diagnostic yield of testing for Fabry disease in isolated small fiber neuropathy patients has never been systematically investigated. Our aim is to determine the presence of Fabry disease in patients with small fiber neuropathy.

Methods: Patients referred to our institute, who met the criteria for isolated small fiber neuropathy were tested for Fabry disease by measurement of alpha-Galactosidase A activity in blood, lysosomal globotriaosylsphingosine in urine and analysis on possible GLA gene mutations.

Results: 725 patients diagnosed with small fiber neuropathy were screened for Fabry disease. No skin abnormalities were seen except for redness of the hands or feet in 30.9% of the patients. Alfa-Galactosidase A activity was tested in all 725 patients and showed diminished activity in eight patients. Lysosomal globotriaosylsphingosine was examined in 509 patients and was normal in all tested individuals. Screening of GLA for mutations was performed for 440 patients, including those with diminished α-Galactosidase A activity. Thirteen patients showed a GLA gene variant. One likely pathogenic variant was found in a female patient. The diagnosis Fabry disease could not be confirmed over time in this patient. Eventually none of the patients were diagnosed with Fabry disease.

Conclusions: In patients with isolated small fiber neuropathy, and no other signs compatible with Fabry disease, the diagnostic yield of testing for Fabry disease is extremely low. Testing for Fabry disease should be considered only in cases with additional characteristics, such as childhood onset, cardiovascular disease, renal failure, or typical skin lesions.

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Conflict of interest statement

Competing Interests: The authors of this manuscript have the following competing interests: BTAG reports a grant from the Prinses Beatrix Spierfonds (W.OR12-01), outside the submitted work. JGJH reports no disclosure. EEW reports no disclosure. HJMS reports no disclosure. AW reports no disclosure. ISJM reports grants from GBS/CIDP foundation international for PeriNomS study and from European Union 7th Framework Programme (grant agreement no. 602273, 2013); Participation in steering committees of the Talecris ICE Study, CSL Behring, LFB, Novartis and Octapharma (a research foundation at the University of Maastricht received the honoraria on behalf of dr. Merkies), outside the submitted work. CGF reports grants from European Union 7th Framework Programme (grant agreement no. 602273, 2013), outside the submitted work, and the Prinses Beatrix Spierfonds (W.OR12-01), outside the submitted work. MMG reports a grant from European Union 7th Framework Programme (grant agreement no. 602273, 2013), outside the submitted work. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1

Fig 1. Diagnostic algorithm for confirming Fabry disease in SFN patients.

(A) Diagnostic algorithm for men. (B) Diagnostic algorithm for women. α-Gal A: α-galactosidase A, FD: Fabry disease, Lyso-GB3: lysosomal globotriaosylceramide. a Abnormal findings of the GLA gene include class 3 variants (uncertain to be pathogenic), class 4 variants (likely to be pathogenic), and class 5 variants (certain pathogenic). b The diagnosis FD is confirmed in women when the abnormal findings of the GLA gene complemented with abnormal findings in the biochemical assessment (α-Gal A and Lyso-GB3).

Fig 2

Fig 2. Small fiber neuropathy patients analyzed for Fabry disease in the Maastricht University Medical Center.

Illustration of the outcome of investigations to confirm the diagnosis of Fabry disease. α-Gal A: α-galactosidase A, Lyso-GB3: lysosomal globotriaosylceramide, FD: Fabry disease, SFN: small fiber neuropathy. a Missing data. b The measurement of lyso-GB3 excretion in urine was incorporated in our workflow for SFN patients from April 2012. c GLA gene sequencing was performed in all women, and in males in case of reduced α-Gal A enzyme activity. d These includes the class 2 variants (unlikely to be pathogenic) and the class 3 variants (uncertain to be pathogenic).

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