Anderson-Fabry disease in heart failure.
Anderson-Fabry disease in heart failure.
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DOI：
10.1007/s12551-018-0432-5
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发表时间：
2018-08-01
影响因子：
--
通讯作者：
Elliott, P M
中科院分区：
文献类型：
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作者：
Akhtar, M M;Elliott, P M
Anderson-Fabry病是一种X-连锁溶酶体贮积症，由GLA基因突变引起，导致α-半乳糖苷酶A缺乏。据报道，法布里病的全球发病率在1/40，000 - 117，000的范围内，尽管在识别症状和延迟或漏诊的情况下，该值可能被显著低估。α-半乳糖苷酶A的缺乏导致中性鞘糖脂如神经酰胺三己糖苷（Gb 3）在各种组织（包括血管内皮、肾、心脏、眼睛、皮肤和神经系统）内的溶酶体中的积累。Gb 3蓄积通过释放促炎细胞因子、生长促进因子和氧化应激诱导病理学，导致心肌细胞外基质重塑、左心室肥大（LVH）、血管功能障碍和间质纤维化。心脏受累表现为心室肥大、收缩和舒张功能障碍、瓣膜异常和传导组织疾病在AFD中很常见，并且与心力衰竭、心源性猝死和卒中相关死亡的相当大的心血管发病率和死亡率相关。
Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene that result in deficiency of the enzyme alpha-galactosidase A. The worldwide incidence of Fabry's disease is reported to be in the range of 1 in 40,000-117,000, although this value may be a significant underestimate given under recognition of symptoms and delayed or missed diagnosis. Deficiency in alpha-galactosidase A causes an accumulation of neutral glycosphingolipids such as globotriaosylceramide (Gb3) in lysosomes within various tissues including the vascular endothelium, kidneys, heart, eyes, skin and nervous system. Gb3 accumulation induces pathology via the release of pro-inflammatory cytokines, growth-promoting factors and by oxidative stress, resulting in myocardial extracellular matrix remodelling, left ventricular hypertrophy (LVH), vascular dysfunction and interstitial fibrosis. Cardiac involvement manifesting as ventricular hypertrophy, systolic and diastolic dysfunction, valvular abnormalities and conduction tissue disease is common in AFD and is associated with considerable cardiovascular morbidity and mortality from heart failure, sudden cardiac death and stroke-related death.