目的:法布里病是一种罕见的X连锁代谢紊乱,其特征是α-半乳糖苷酶A缺乏。主要症状是四肢疼痛,而在更先进的阶段,表现包括肥厚型心肌病,心律失常,蛋白尿,慢性肾功能不全,中风,和听力损失。当没有诊断和治疗时,法布里病导致早期死亡。没有专门设计用于描述法布里病的肌肉骨骼表现的研究。
方法:我们对在法布里病转诊中心接受随访的患者进行了一项单中心回顾性研究。我们描述了肌肉骨骼表现并分析了鉴别诊断。
结果:我们的研究包括20个家庭的40名患者,包括25名女性,平均年龄44.2岁(范围,20-76岁)和15名男性,平均年龄40.1岁(范围,16-61岁)。诊断为法布里病的平均年龄为37.2岁(范围,7-71岁)女性和26.9岁(范围,9-51岁)在男性中。对10名(40%)女性和12名(80%)男性进行了特异性酶替代疗法。肌肉骨骼表现如下:过去或现在的四肢疼痛(13名女性和10名男性),合并一些四肢血管舒缩障碍和毛细血管扩张症患者;运动不耐受(12名女性和12名男性);骨质疏松性骨折(2名45岁和44岁的兄弟,分别);骨质疏松症(3名女性,57岁、63岁和75岁,分别),导致年龄最大的患者死亡;骨量减少(2名38岁和47岁的女性,分别;和1名43岁的男性);Charcot足和淋巴水肿伴严重感染并发症(4名40岁以上的男性),下肢无血管坏死2例;脚趾截肢(3例);双侧下肢截肢(1例);下肢异常细长(女性5例,男性8例);急性痛风(男性3例,严重慢性肾功能衰竭);腕管综合征(女性1例,男性1例,年龄均小于40岁)。早期做出的错误诊断,导致延迟法布里病的识别,包括风湿热(2名女性和2名男性),成长的痛苦(2个男性),瘫痪疼痛(1名女性),下肢冻疮(1名女性),和红斑(1名女性)。成年后,做出以下错误诊断:干燥综合征和/或干燥综合征(6名女性),系统性硬化症(1名男性),自主神经障碍(1名女性),家族性地中海热(1名女性)。
结论:法布里病的诊断通常会延迟,由于与更常见的疾病混淆。肌肉骨骼表现可能构成表现症状。过去或现在的四肢疼痛是典型的。骨质疏松可早期发展并变得严重。加上家族史,肌肉骨骼表现的存在可以通过提示男性中的α-半乳糖苷酶测定和女性中的基因检测来导致正确的诊断。法布里病通常是肌肉骨骼表现的原因,其中最常见的是四肢疼痛和骨质疏松症。这些表现可能是开创性的,并导致诊断性的流浪。它们需要特定的治疗策略。
OBJECTIVE: Fabry disease is a rare X-linked metabolic disorder characterized by a deficiency in the enzyme alpha-galactosidase A. Both males and females can be affected. The main presenting symptom is pain in the extremities, whereas at a more advanced stage, the manifestations include hypertrophic cardiomyopathy, cardiac dysrhythmia, proteinuria, chronic kidney dysfunction, stroke, and hearing loss. When not diagnosed and treated, Fabry disease causes early death. No studies specifically designed to describe the musculoskeletal manifestations of Fabry disease are available.
METHODS: We conducted a single-center retrospective study of patients receiving follow-up at a Fabry disease referral center. We described the musculoskeletal manifestations and analyzed the differential diagnoses.
RESULTS: Our study included 40 patients belonging to 20 families, including 25 females with a mean age of 44.2 years (range, 20-76 years) and 15 males with a mean age of 40.1 years (range, 16-61 years). Mean age at the diagnosis of Fabry disease was 37.2 years (range, 7-71 years) in the females and 26.9 years (range, 9-51 years) in the males. Specific enzyme replacement therapy was given to 10 (40%) females and 12 (80%) males. Musculoskeletal manifestations were as follows: past or present pain in the extremities (13 females and 10 males), combined in some patients with vasomotor disorders in the extremities and telangiectasia; exercise intolerance (12 females and 12 males); osteoporotic fractures (2 brothers aged 45 and 44 years, respectively); osteoporosis (3 females, aged 57, 63, and 75 years, respectively), which contributed to death in the oldest patient; osteopenia (2 females aged 38 and 47 years, respectively; and 1 male aged 43 years); Charcot foot and lymphedema with serious infectious complications (4 males older than 40 years), with avascular osteonecrosis of the lower limbs in 2 cases; toe amputations (3 cases); bilateral lower-limb amputation (1 case); abnormally slender lower limbs (5 females and 8 males); acute gout (3 males with severe chronic kidney failure); and carpal tunnel syndrome (1 female and 1 male, both younger than 40 years). Mistaken diagnoses that were made at an early stage, contributing to delay the identification of Fabry disease, included rheumatic fever (2 females and 2 males), growing pains (2 males), pain with paralysis (1 female), chilblains of the lower limbs (1 female), and erythermalgia (1 female). In adulthood, the following mistaken diagnoses were made: Sjögren\'s syndrome and/or sicca syndrome (6 females), systemic sclerosis (1 male), dysautonomia (1 female), and familial Mediterranean fever (1 female).
CONCLUSIONS: The diagnosis of Fabry disease is usually delayed, due to confusion with more common disorders. Musculoskeletal manifestations may constitute the presenting symptoms. Past or present pain in the extremities is typical. Osteoporosis may develop early and become severe. Together with the family history, the presence of musculoskeletal manifestations can lead to the correct diagnosis by prompting alpha-galactosidase assays in males and genetic testing in females. Fabry disease is often responsible for musculoskeletal manifestations, of which the most common are pain in the extremities and osteoporosis. These manifestations can be inaugural and lead to diagnostic wanderings. They require specific treatment strategies.