van der Tol L, Cassiman David, Houge Gunnar, Janssen Mirian C, Lachmann Robin H, Linthorst Gabor E, Ramaswami Uma, Sommer Claudia, Tøndel Camilla, West Michael L, Weidemann Frank, Wijburg Frits A, Svarstad Einar, Hollak Carla Em, Biegstraaten Marieke
Department of Internal Medicine, Division Endocrinology and Metabolism, Amsterdam lysosome centre 'Sphinx', Academic Medical Center, University of Amsterdam, Room F5-166, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
JIMD Rep. 2014;17:83-90. doi: 10.1007/8904_2014_342. Epub 2014 Sep 16.
Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the α-galactosidase A (GLA) gene may be unclear. This uncertainty often leads to considerable distress and inappropriate counselling and treatment. We developed a clinical approach for these individuals with an uncertain diagnosis of FD.
A document was presented to an FD expert panel with background information based on clinical experience and the literature, followed by an online survey and a written recommendation.
The 13 experts agreed that the recommendation is intended for individuals with neuropathic pain, AK and/or CV only, i.e. without kidney, heart or brain disease, with an uncertain diagnosis of FD. Only in the presence of FD-specific neuropathic pain (small fibre neuropathy with FD-specific pattern), AK (FD-specific localisations) or CV (without CV inducing medication), FD is confirmed. When these features have a non-specific pattern, there is insufficient evidence for FD. If no alternative diagnosis is found, follow-up is recommended.
In individuals with an uncertain diagnosis of FD, the presence of an FD-specific pattern of CV, AK or neuropathic pain is sufficient to confirm the diagnosis of FD. When these features are non-specific, a definite diagnosis cannot (yet) be established and follow-up is indicated. ERT should be considered only in those patients with a confirmed diagnosis of FD.
患有神经性疼痛、血管角质瘤（AK）和/或涡状角膜病变（CV）的个体可能会接受法布里病（FD）检测。典型的FD具有这些特征的特定模式。当患者呈现非特异性模式时，α-半乳糖苷酶A（GLA）基因变异的致病性可能不明确。这种不确定性常常导致相当大的痛苦以及不适当的咨询和治疗。我们针对这些FD诊断不确定的个体制定了一种临床方法。
根据临床经验和文献，向一个FD专家小组提交了一份包含背景信息的文件，随后进行了在线调查并给出了书面建议。
13位专家一致认为，该建议仅适用于患有神经性疼痛、AK和/或CV的个体，即没有肾脏、心脏或脑部疾病且FD诊断不确定的个体。仅在存在FD特异性神经性疼痛（具有FD特异性模式的小纤维神经病变）、AK（FD特异性定位）或CV（无诱发CV的药物）时，才能确诊FD。当这些特征呈现非特异性模式时，FD的证据不足。如果未发现其他诊断，则建议进行随访。
对于FD诊断不确定的个体，存在CV、AK或神经性疼痛的FD特异性模式足以确诊FD。当这些特征是非特异性时，（目前）无法确立明确诊断，应进行随访。仅在确诊为FD的患者中才应考虑酶替代疗法（ERT）。
