Smid B E, van der Tol L, Cecchi F, Elliott P M, Hughes D A, Linthorst G E, Timmermans J, Weidemann F, West M L, Biegstraaten M, Lekanne Deprez R H, Florquin S, Postema P G, Tomberli B, van der Wal A C, van den Bergh Weerman M A, Hollak C E
Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical and Experimental Medicine, University of Florence, Italy.
Int J Cardiol. 2014 Dec 15;177(2):400-8. doi: 10.1016/j.ijcard.2014.09.001. Epub 2014 Sep 20.
Screening in subjects with left ventricular hypertrophy (LVH) reveals a high prevalence of Fabry disease (FD). Often, a diagnosis is uncertain because characteristic clinical features are absent and genetic variants of unknown significance (GVUS) in the α-galactosidase A (GLA) gene are identified. This carries a risk of misdiagnosis, inappropriate counselling and extremely expensive treatment. We developed a diagnostic algorithm for adults with LVH (maximal wall thickness (MWT) of >12 mm), GLA GVUS and an uncertain diagnosis of FD.
A Delphi method was used to reach a consensus between FD experts. We performed a systematic review selecting criteria on electrocardiogram, MRI and echocardiography to confirm or exclude FD. Criteria for a definite or uncertain diagnosis and a gold standard were defined.
A definite diagnosis of FD was defined as follows: a GLA mutation with ≤ 5% GLA activity (leucocytes, mean of reference value, males only) with ≥ 1 characteristic FD symptom or sign (neuropathic pain, cornea verticillata, angiokeratoma) or increased plasma (lyso)Gb3 (classical male range) or family members with definite FD. Subjects with LVH failing these criteria have a GVUS and an uncertain diagnosis. The gold standard was defined as characteristic storage in an endomyocardial biopsy on electron microscopy. Abnormally low voltages on ECG and severe LVH (MWT>15 mm) <20 years exclude FD. Other criteria were rejected due to insufficient evidence.
In adults with unexplained LVH and a GLA GVUS, severe LVH at young age and low voltages on ECG exclude FD. If absent, an endomyocardial biopsy with electron microscopy should be performed.
对左心室肥厚（LVH）患者进行筛查发现，法布里病（FD）的患病率很高。通常，由于缺乏特征性临床特征且在α-半乳糖苷酶A（GLA）基因中发现意义不明的基因变异（GVUS），诊断往往不确定。这存在误诊、不适当咨询和极其昂贵治疗的风险。我们针对患有LVH（最大壁厚（MWT）>12mm）、GLA GVUS且FD诊断不确定的成年人开发了一种诊断算法。
采用德尔菲法在FD专家之间达成共识。我们进行了一项系统评价，选择心电图、MRI和超声心动图的标准来确认或排除FD。定义了明确或不确定诊断的标准以及金标准。
FD的明确诊断定义如下：GLA突变且GLA活性≤5%（白细胞，参考值均值，仅男性），伴有≥1种特征性FD症状或体征（神经性疼痛、涡状角膜、血管角质瘤）或血浆（溶酶体）Gb3升高（经典男性范围）或有明确FD的家庭成员。未达到这些标准的LVH患者存在GVUS且诊断不确定。金标准定义为心内膜活检电子显微镜下的特征性储存。心电图低电压和严重LVH（MWT>15mm）且年龄<20岁可排除FD。由于证据不足，其他标准被排除。
在患有无法解释的LVH和GLA GVUS的成年人中，年轻时严重LVH和心电图低电压可排除FD。如果不存在这些情况，则应进行心内膜活检及电子显微镜检查。
