Romano Candela, Wells Joel, Stanzione Nicholas, Kimonis Virginia
Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, CA, USA.
Medical Director of the Comprehensive Hip Center Program & Hip Preservation Center, Baylor Scott & White McKinney Texas, Orthopedic Surgery Texas A&M School of Medicine, USA.
Mol Genet Metab Rep. 2025 Apr 12;43:101219. doi: 10.1016/j.ymgmr.2025.101219. eCollection 2025 Jun.
Fabry disease is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the gene, which encodes for the α-galactosidase A enzyme responsible for degrading globotriaosylceramide. Its deficiency leads to the accumulation of GL3 in lysosomes, resulting in progressive multi-organ involvement, with predilection for the heart and kidneys. Clinical features associated with Fabry disease include acroparesthesia, angiokeratomas, hypohidrosis, corneal whorls, chronic kidney disease, cardiomyopathy, and strokes. Osteopenia and osteoporosis are less known complications, with rare reported cases of avascular necrosis of the hips. We report bilateral avascular necrosis in a 40-year-old-man diagnosed with Fabry at the age of 25 years. He carriers the familiar p.G328V pathogenic variant. His Fabry features includes acroparesthesia, angiokeratomas, hypohidrosis, temperature and exercise intolerance, pain crises, abdominal pain and diarrhea, tinnitus, hearing loss, hypertrophic cardiomyopathy, palpitations, and chest pain. Family history reveals Fabry disease affecting multiple maternal relatives. The patient was recently diagnosed with avascular necrosis of the right hip requiring total arthroplasty due to failure of conservative treatment. Nine months later, he developed left hip pain attributed to avascular necrosis, also treated with total arthroplasty. This case highlights a rare skeletal complication of Fabry disease, underscoring the need for early diagnosis, optimizing treatment of Fabry disease, managing atypical comorbidities, and vigilant monitoring of bone health.
法布里病是一种罕见的X连锁溶酶体贮积症，由该基因的致病变异引起，该基因编码负责降解球三糖神经酰胺的α-半乳糖苷酶A。其缺乏导致溶酶体中GL3的积累，导致进行性多器官受累，以心脏和肾脏受累为主。与法布里病相关的临床特征包括肢端感觉异常、血管角质瘤、少汗症、角膜涡状浑浊、慢性肾病、心肌病和中风。骨质减少和骨质疏松是鲜为人知的并发症，髋部无血管性坏死的报道病例罕见。我们报告了一名40岁男性双侧无血管性坏死病例，该患者25岁时被诊断为法布里病。他携带常见的p.G328V致病变异。他的法布里病特征包括肢端感觉异常、血管角质瘤、少汗症、不耐温度和运动、疼痛危象、腹痛和腹泻、耳鸣、听力丧失、肥厚型心肌病、心悸和胸痛。家族史显示法布里病影响多名母系亲属。该患者最近被诊断为右髋无血管性坏死，由于保守治疗失败需要进行全关节置换术。九个月后，他因无血管性坏死出现左髋疼痛，也接受了全关节置换术治疗。该病例突出了法布里病一种罕见的骨骼并发症，强调了早期诊断、优化法布里病治疗、管理非典型合并症以及密切监测骨骼健康的必要性。
