Okada Jun, Hossain Mohammad Arif, Wu Chen, Miyajima Takashi, Yanagisawa Hiroko, Akiyama Keiko, Eto Yoshikatsu
Asakadai Central General Hospital, Asaka City, Japan.
Advanced Clinical Research Center, Institute of Neurological Disorders, Shin-Yurigaoka General Hospital, Kawasaki, Kanagawa, Japan.
Mol Genet Metab Rep. 2017 Dec 22;14:68-72. doi: 10.1016/j.ymgmr.2017.12.004. eCollection 2018 Mar.
Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-gal A), leading to the progressive accumulation of glycosphingolipids. Classical hemizygous males usually present symptoms, including pain and paresthesia in the extremities, angiokeratoma, hypo- or anhidrosis, abdominal pain, cornea verticillata, early stroke, tinnitus, and/or hearing loss, during early childhood or adolescence. Moreover, proteinuria, renal impairment, and cardiac hypertrophy can appear with age. Enzyme replacement is the most common therapy for Fabry disease at present which has been approved in Japan since 2004. We report a case involving a 27-year-old male with extreme terminal pain, anhidrosis, abdominal pain, tinnitus, hearing impairment, cornea verticillata, and recurrent huge ulcers in the lower extremities. At the age of 16 years, he was diagnosed with Fabry disease with a positive family history and very low α-gal A activity. He then received enzyme replacement therapy (ERT) with recombinant human agalsidase beta at 1 mg/kg every 2 weeks for 10 years. Throughout the course of ERT, his leg ulcers recurred, and massive excretion of urinary globotriaosylceramide and plasma globotriaosylsphingosine was observed. Electron microscopy of the venous tissue in the regions of the ulcer showed massive typical zebra bodies in the vascular wall smooth muscle cells.
法布里病是一种X连锁溶酶体贮积症，由α-半乳糖苷酶A（α-gal A）缺乏引起，导致糖鞘脂进行性蓄积。典型的半合子男性通常在幼儿期或青春期出现症状，包括四肢疼痛和感觉异常、血管角质瘤、少汗或无汗、腹痛、涡状角膜、早期中风、耳鸣和/或听力丧失。此外，蛋白尿、肾功能损害和心脏肥大可随年龄出现。酶替代疗法是目前治疗法布里病最常用的方法，自2004年起在日本获得批准。我们报告一例病例，患者为一名27岁男性，患有极度终末期疼痛、无汗、腹痛、耳鸣、听力障碍、涡状角膜以及下肢反复出现巨大溃疡。16岁时，他被诊断为法布里病，家族史阳性，α-gal A活性极低。随后他接受了重组人α-半乳糖苷酶β的酶替代疗法（ERT），每2周1mg/kg，持续10年。在ERT治疗过程中，他的腿部溃疡复发，观察到尿球三糖神经酰胺和血浆球三糖神经鞘氨醇大量排泄。溃疡部位静脉组织的电子显微镜检查显示血管壁平滑肌细胞中有大量典型的斑马小体。
