Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Mol Genet Genomic Med. 2020 Oct;8(10):e1454. doi: 10.1002/mgg3.1454. Epub 2020 Aug 14.
Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to the absent or deficient activity of lysosomal hydrolase a-galactosidase A (α-Gal A), which leads to the accumulation of its substrates in various organs and tissues. Classic clinical manifestations include angiokeratomas, proteinuria, renal failure, neuropathic pain, and left ventricular hypertrophy. Fever is one of the rare symptoms that may occur during FD.
Three Chinese Han patients with FD referred to Peking Union Medical College Hospital were reported. The complete medical records were established, and detailed data were collected. Whole-exome sequencing by next-generation sequencing and α-Gal A enzyme activity assay were performed to confirm the diagnosis.
These three patients all presented with recurrent fever of unknown origin initially, accompanied with arthralgia/arthritis and other symptoms. We identified two known variants in the GLA gene, c.1176_1179delGAAG and c.782G>A (p.G261D), and a novel variant c.440G>A (p.G147E) which is likely pathogenic in our patient.
FD should be considered as a rare cause of recurrent fever of unknown origin. The coexistence of gene variants related to systemic autoinflammatory diseases may make the clinical phenotypes of FD more complex and prone to recurrent fever.
法布里病（FD）是一种罕见的 X 连锁溶酶体贮积病，由于溶酶体水解酶α-半乳糖苷酶 A（α-Gal A）的缺失或活性不足，导致其底物在各种器官和组织中积累。经典的临床表现包括血管角质瘤、蛋白尿、肾衰竭、神经性疼痛和左心室肥厚。发热是 FD 期间可能发生的罕见症状之一。
报告了 3 例就诊于北京协和医院的 FD 汉族患者。建立完整的病历，并收集详细数据。通过下一代测序进行全外显子组测序和α-Gal A 酶活性测定以确认诊断。
这 3 例患者最初均表现为不明原因的反复发热，伴有关节痛/关节炎等症状。我们在 GLA 基因中发现了 2 个已知变异，c.1176_1179delGAAG 和 c.782G>A（p.G261D），以及一个可能致病的新变异 c.440G>A（p.G147E）。
FD 应被视为不明原因反复发热的罕见原因。与系统性自身炎症性疾病相关的基因变异的共存可能使 FD 的临床表型更加复杂，更容易出现反复发热。
