Skin Globotriaosylceramide 3 Deposits Are Specific to Fabry Disease with Classical Mutations and Associated with Small Fibre Neuropathy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Jul 4

PMID 28672034

Citations 15

Authors

Rocco Liguori

Alex Incensi

Silvia De Pasqua

Renzo Mignani

Enrico Fileccia

Marisa Santostefano

Elena Biagini

Claudio Rapezzi

Silvia Palmieri

Ilaria Romani

Walter Borsini

Alessandro Burlina

Roberto Bombardi

Marco Caprini

Patrizia Avoni

Vincenzo Donadio

Affiliations

Soon will be listed here.

Abstract

Background: Fabry 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.

Methods: we 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.

Results: 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 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.

Conclusions: 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.

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