Department of Neuropediatrics, University Children's Hospital, Tübingen, Germany.
Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
J Cutan Pathol. 2022 Mar;49(3):293-298. doi: 10.1111/cup.14154. Epub 2021 Nov 7.
Angiokeratoma corporis diffusum (ACD) was long thought to be a specific dermal sign of Fabry disease (FD, X-linked alpha-galactosidase A [GLA] deficiency). However, other lysosomal storage diseases (LSDs) have also been identified as triggers of ACD. Generalized vasculopathy is an important pathogenetic factor in FD and may also lead to the acroparesthesia (AP) often predominant in FD. We report on an 85-year-old woman with ACD present since her youth and associated with severe AP. Ultrastructure of the dermal lesion showed no lysosomal involvement, but the absence of the basement membrane of the endothelial cells of the capillary vessels was noteworthy. Repeated analyses of the GLA gene revealed no evidence of FD. Whole-exome sequencing was negative for FD and other LSDs, and allowed us to also study FD-related intronic regions of the GLA gene. This is the first report of a patient with FD-like ACD with an endothelial abnormality, otherwise unexplained vasculopathy and severe AP, which are not due to FD or another LSD. Based on family history, another genetic, yet unidentified, defect may cause the disease in this patient. In unexplained ACD, extended genetic analysis is required to exclude particular pathogenic variants of the GLA gene and other genes.
弥漫性躯体血管角化瘤（ACD）长期以来被认为是法布里病（FD，X 连锁α-半乳糖苷酶 A [GLA] 缺乏症）的一种特异性皮肤标志。然而，其他溶酶体贮积病（LSD）也被确定为 ACD 的触发因素。全身性血管病是 FD 的一个重要发病因素，也可能导致 FD 中经常占主导地位的肢端感觉异常（AP）。我们报告了一例 85 岁女性，自年轻时即存在 ACD，并伴有严重的 AP。皮肤病变的超微结构显示无溶酶体受累，但毛细血管内皮细胞的基底膜缺失值得注意。GLA 基因的反复分析未发现 FD 的证据。外显子组测序结果 FD 和其他 LSD 均为阴性，并允许我们研究 FD 相关的 GLA 基因内含子区域。这是首例报道的 FD 样 ACD 患者，存在内皮异常、其他原因不明的血管病和严重的 AP，这不是由 FD 或其他 LSD 引起的。基于家族史，另一种遗传的、尚未确定的缺陷可能导致该患者患病。对于原因不明的 ACD，需要进行扩展的基因分析以排除 GLA 基因和其他基因的特定致病性变异。
