The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease a cross-sectional study of a large cohort of clinically affected heterozygous women
The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease a cross-sectional study of a large cohort of clinically affected heterozygous women
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DOI：
10.1097/01.md.0000178976.62537.6b
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发表时间：
2005-09-01
期刊：
影响因子：
1.6
通讯作者：
Schiffmann, R
中科院分区：
文献类型：
--
作者：
Gupta, S;Ries, M;Schiffmann, R
Fabry病是一种罕见的X连锁溶酶体储存障碍，原因是α-半乳糖苷酶A(α-GalA)活性不足，导致糖鞘糖脂，特别是球三糖神经酰胺(GBA)在全身细胞中储存，在半合子男性和一些杂合子女性中导致危及生命的肾、心脏和脑血管并发症。杂合子的疾病表现正得到越来越多的认识，但关于其程度和严重程度的定量前瞻性数据有限。在一项为期7天的研究中，对61名有Fabry病症状和体征的女性进行了前瞻性的临床和实验室评估。分析包括病史和生理、神经、心脏和眼科评估；实验室评估；肾功能测试；头部磁共振成像(MRI)和磁共振血管成像(MRA)；以及与Fabry相关的血液和尿液测试，包括血液和尿液中的GB(3)水平、皮肤活检和α-GalA基因的DNA基因型分析，以确定致病突变。通过有效问卷和日记记录患者的生活质量、疼痛和伴随用药情况。所有患者的血浆Gb3水平均正常，仅1例患者真皮浅血管内皮细胞内可见储存物质。在57例确诊为Fabry基因的患者中，有52例(91%)记录到心脏、肾脏或脑血管异常。这些异常包括心电图异常38例(73%)，超声心动图异常8例(14%)，蛋白尿23例(61%)，估计肾小球滤过率低24例(42%)，MRI异常4例(7%)，MRA异常10例(20%)。在57名患者中，分别有63%和82%的患者出现了血管性角化瘤和角膜上皮病变。尽管血浆和皮肤血管内皮细胞中几乎没有储存物质，但这些患有Fabry病的女性患者表现出广泛的临床异常。需要开发用于评估特定治疗的有用的结果衡量标准。仅限于受同质性影响的受试者的研究是可能的。
Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient activity of alpha-galactosidase A (alpha-Gal A) resulting in the storage of glycosphingolipids, especially globotriaosylceramide (GbA in cells throughout the body, causing life-threatening renal, cardiac, and cerebrovascular complications in hemizygous males and some heterozygous females. Disease manifestations in heterozygotes are being recognized increasingly, but quantitative prospective data on their extent and severity are limited.Prospective clinical and laboratory assessments were performed in a 7-day study of 61 women with signs and symptoms of Fabry disease. Analyses included medical history and physical, neurologic, cardiac, and ophthalmologic assessments; laboratory assessments; renal function tests; magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head; and Fabry-related blood and urine tests, including Gb(3) levels in blood and urine, skin biopsies, and DNA genotype analysis of the alpha-Gal A gene to identify causative mutations. Quality of life, pain and concomitant medication were documented using validated questionnaires and diaries.All patients had normal Gb3 levels in plasma; only 1 patient had visible storage material in the superficial dermal vascular endothelial cells. Cardiac, renal, or cerebrovascular abnormalities were documented in 52 of the 57 patients (91%) with confirmed Fabry genotypes. These included electrocardiographic abnormalities in 38 of 52 patients (73%), echocardiographic abnormalities in 8 of 57 (14%), proteinuria (> 150 g protein/24-h urine) in 23 of 3 8 (61%), low estimated glomerular filtration rate (< 90 mL/min per 1.73 m(2)) in 24 of 57 (42%), abnormal MRI in 4 of 54 (7%), and abnormal MRA in 10 of 50 patients (20%). Angiokeratomas and corneal epitheliopathy were documented in 63% and 82% of the 57 patients, respectively.Despite the virtual absence of storage material in plasma and skin vascular endothelial cells, this population of women with Fabry disease exhibited a wide spectrum of clinical abnormalities. Useful outcome measures for assessment of specific therapies need to be developed. Studies limited to homogeneously affected subjects may be possible.