Kalliokoski R J, Kantola I, Kalliokoski K K, Engblom E, Sundell J, Hannukainen J C, Janatuinen T, Raitakari O T, Knuuti J, Penttinen M, Viikari J, Nuutila P
Turku PET Centre, University of Turku, PO Box 52, FIN-20521 Turku, Finland.
J Inherit Metab Dis. 2006 Feb;29(1):112-8. doi: 10.1007/s10545-006-0221-3.
Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.
法布里病（麦库西克编号301500）是一种X连锁溶酶体贮积症，继发于α-半乳糖苷酶A活性缺乏，导致球三糖神经酰胺（Gb(3)）及相关糖鞘脂广泛蓄积，尤其是在血管平滑肌和内皮细胞中。我们最近发现，法布里病患者的心肌灌注储备显著降低。因此，在本研究中，我们调查了酶替代疗法（ERT）是否能改善这一情况。10例确诊为法布里病的患者（7例男性，3例女性；平均年龄34岁，范围19 - 49岁）被批准参加这项非对照、开放标签研究。通过正电子发射断层扫描和放射性水在静息状态及双嘧达莫诱发的充血期间测量心肌灌注。心肌灌注储备计算为最大灌注与静息灌注的比值。在接受重组人α-半乳糖苷酶A（法布赞，健赞公司）进行ERT治疗6个月和12个月前后进行灌注测量。血浆Gb(3)浓度显著降低，患者报告ERT治疗后感觉更好，疼痛减轻。然而，在ERT治疗期间，静息或双嘧达莫刺激的心肌灌注以及心肌灌注储备均未改变。治疗前相对室壁厚度与治疗后血流储备变化呈负相关（r = -0.76，p = 0.05），与治疗后最小冠状动脉阻力变化呈正相关（r = 0.80，p = 0.03）。本研究表明，尽管血浆Gb(3)浓度降低，但12个月的ERT治疗并未改善心肌灌注储备。然而，治疗反应的个体差异很大，结果表明治疗的成功可能取决于心脏肥大的程度。
