Abstract
BackgroundFabry Disease (FD) is characterized by globotriaosylceramide-3 (Gb3) accumulation in several tissues and a small fibre neuropathy (SFN), however the underlying mechanisms are poorly known. This study aimed to: 1) ascertain the presence of Gb3 deposits in skin samples, by an immunofluorescence method collected from FD patients with classical GLA mutations or late-onset FD variants or GLA polymorphisms; 2) correlate skin GB3 deposits with skin innervation.Methodswe studied 52 genetically-defined FD patients (32 with classical GLA mutations and 20 with late-onset variants or GLA polymorphisms), 15 patients with SFN associated with a specific cause and 22 healthy controls. Subjects underwent skin biopsy to evaluate Gb3 deposits and epi-dermal innervation.ResultsSkin Gb3 deposits were found in all FD patients with classical GLA mutations but never in FD patients with late-onset variants or GLA polymorphisms or in patients with SFN and healthy controls. Abnormal deposits were found inside different skin structures but never inside axons. FD patients with GB3 deposits showed lower skin innervation than FD patients with late-onset variants or polymorphisms.Conclusions1) Skin Gb3 deposits are specific to FD patients with classical GLA mutations; 2) Gb3 deposits were associated with lower skin innervation but they were not found inside axons, suggesting an indirect damage on peripheral small fibre innervation.
Highlights
Fabry Disease (FD) is a rare x-linked disorder[1] characterized by an abnormal function of the lysosomal enzyme alpha-galactosidase A (GLA)[2,3], involved in the cleavage of galactose residuals of globotriaosylceramide-3 (Gb3)[4]
Skin Gb3 deposits were found in all FD patients with classical GLA mutations but never in FD patients with late-onset variants or GLA polymorphisms or in patients with small fibre neuropathy (SFN) and healthy controls
1) Skin Gb3 deposits are specific to FD patients with classical GLA mutations; 2) Gb3 deposits were associated with lower skin innervation but they were not found inside axons, suggesting an indirect damage on peripheral small fibre innervation
Summary
Fabry Disease (FD) is a rare x-linked disorder[1] characterized by an abnormal function of the lysosomal enzyme alpha-galactosidase A (GLA)[2,3], involved in the cleavage of galactose residuals of globotriaosylceramide-3 (Gb3)[4]. Skin Gb3 deposits have been demonstrated by using complex techniques such as electron microscopy[13] but they can be detected by more simple and rapid techniques such as light microscopy[14,15]. By using this latter technique skin Gb3 deposits were not found in all analysed patients[15,16], preventing the use of this approach for diagnostic purposes. Fabry Disease (FD) is characterized by globotriaosylceramide-3 (Gb3) accumulation in several tissues and a small fibre neuropathy (SFN), the underlying mechanisms are poorly known. This study aimed to: 1) ascertain the presence of Gb3 deposits in skin samples, by an immunofluorescence method collected from FD patients with classical GLA mutations or late-onset FD variants or GLA polymorphisms; 2) correlate skin GB3 deposits with skin innervation.
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