皮肤Globotriaosylceramide 3沉积物是具有经典突变的法布里病所特有的，并且与小纤维神经病变相关。
Skin globotriaosylceramide 3 deposits are specific to Fabry disease with classical mutations and associated with small fibre neuropathy.
作者信息
Liguori Rocco, Incensi Alex, de Pasqua Silvia, Mignani Renzo, Fileccia Enrico, Santostefano Marisa, Biagini Elena, Rapezzi Claudio, Palmieri Silvia, Romani Ilaria, Borsini Walter, Burlina Alessandro, Bombardi Roberto, Caprini Marco, Avoni Patrizia, Donadio Vincenzo
机构信息
IRCCS Institute of Neurological Sciences, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
出版信息
PLoS One. 2017 Jul 3;12(7):e0180581. doi: 10.1371/journal.pone.0180581. eCollection 2017.
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
- 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.
背景
法布里病（FD）的特征是多种组织中存在 globotriaosylceramide-3（Gb3）蓄积以及小纤维神经病变（SFN），但其潜在机制尚不清楚。本研究旨在：1）通过免疫荧光法确定从具有经典 GLA 突变的 FD 患者、迟发性 FD 变异体或 GLA 多态性患者采集的皮肤样本中是否存在 Gb3 沉积物；2）将皮肤 Gb3 沉积物与皮肤神经支配相关联。
方法
我们研究了 52 例基因明确的 FD 患者（32 例具有经典 GLA 突变，20 例具有迟发性变异体或 GLA 多态性）、15 例与特定病因相关的 SFN 患者以及 22 名健康对照。受试者接受皮肤活检以评估 Gb3 沉积物和表皮神经支配。
结果
在所有具有经典 GLA 突变的 FD 患者中均发现皮肤 Gb3 沉积物，但在具有迟发性变异体或 GLA 多态性的 FD 患者、SFN 患者及健康对照中均未发现。在不同皮肤结构内发现了异常沉积物，但在轴突内未发现。具有 Gb3 沉积物的 FD 患者的皮肤神经支配低于具有迟发性变异体或多态性的 FD 患者。
结论
1）皮肤 Gb3 沉积物是具有经典 GLA 突变的 FD 患者所特有的；2）Gb3 沉积物与较低的皮肤神经支配相关，但在轴突内未发现，提示对周围小纤维神经支配有间接损害。
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