Medizinische Klinik und Poliklinik I, University Hospital Würzburg, Würzburg, Germany; Klinikum Vest, Recklinghausen, Germany.
Institut für Röntgendiagnostik, University Hospital Würzburg, Würzburg, Germany; Klinik für Diagnostische und Interventionelle Radiologie, University Hospital Ulm, Ulm, Germany.
Mol Genet Metab. 2019 Feb;126(2):169-182. doi: 10.1016/j.ymgme.2018.11.005. Epub 2018 Nov 12.
Initiation of enzyme replacement therapy (ERT) early in the Fabry disease course may facilitate better outcomes than in patients with advanced disease. Early diagnosis is often hindered by the heterogeneous nature of signs and symptoms, and by the presentation of atypical phenotypes.
The Sophisticated Assessment of Disease Burden in Patients with Fabry Disease study (SOPHIA; ClinicalTrials.gov, NCT01210196) evaluated clinical and diagnostic assessments for early detection of Fabry-related organ pathology in ERT-naïve patients with mild FD symptoms. Assessments included cardiac magnetic resonance imaging with late gadolinium enhancement (LGE-CMR), echocardiography, 24-h Holter electrocardiography, and biomarkers of FD and fibrosis.
35 patients with mean (SD) baseline age of 45.0 (10.2) years were included and assessed at baseline, 12 months, and (optionally) at 24 months. At baseline, LGE-CMR and elevated procollagen III N-terminal propeptide, sphingosine-1-phosphate, and globotriaosylsphingosine were the most prevalent indicators of early Fabry-related pathology. LGE was already present in 58.8% of patients with normal left ventricular mass index. 15.2% of patients showed grade 1 diastolic dysfunction. QRS duration increased from baseline to last observation, particularly in patients with severe baseline fibrosis. Fibrosis progressed from baseline to last observation, especially in patients with baseline LGE ≥ 2.50 mL (3.65 [1.14] mL vs 6.74 [1.10] mL). Statistically significant correlations were found between LGE volume and high-sensitivity troponin T, and between LGE volume and fragments of urinary collagen alpha-1 (I), (III), and (VII), and collagen alpha-3 (V).
Fibrosis may become apparent before left ventricular hypertrophy occurs. LGE-CMR imaging is superior to conventional echocardiography for detecting early cardiomyopathy in FD and, in conjunction with biomarker tests, may help detect early organ involvement in mild FD.
在法布瑞病（Fabry disease，FD）病程早期启动酶替代疗法（ERT）可能比在疾病晚期开始治疗能获得更好的结果。由于体征和症状的异质性以及不典型表型的出现，早期诊断往往受到阻碍。
Sophisticated Assessment of Disease Burden in Patients with Fabry Disease 研究（SOPHIA；ClinicalTrials.gov，NCT01210196）评估了 ERT 初治的、有轻度 FD 症状的患者中用于早期发现与 Fabry 相关的器官病理学的临床和诊断评估。评估包括心脏磁共振成像（CMR）检查（钆延迟增强，LGE-CMR）、超声心动图、24 小时动态心电图和 FD 及纤维化的生物标志物。
35 名平均（标准差）基线年龄为 45.0（10.2）岁的患者被纳入并在基线、12 个月和（可选）24 个月时进行评估。基线时，LGE-CMR 和升高的前胶原 III N 端前肽、神经鞘氨醇-1-磷酸和神经酰胺三己糖苷水平是早期 Fabry 相关病理的最常见指标。在左心室质量指数正常的患者中，已有 58.8%存在 LGE。15.2%的患者出现 1 级舒张功能障碍。QRS 间期从基线到最后一次观察持续增加，尤其是基线纤维化严重的患者。纤维化从基线到最后一次观察进展，特别是基线 LGE≥2.50mL（3.65[1.14]mL 比 6.74[1.10]mL）的患者。在 LGE 体积和高敏肌钙蛋白 T 之间以及 LGE 体积和尿胶原 α-1（I）、（III）和（VII）片段和胶原 α-3（V）之间发现了统计学显著相关性。
纤维化可能在左心室肥厚发生之前变得明显。LGE-CMR 成像优于传统超声心动图，用于检测 FD 中的早期心肌病，与生物标志物检测联合使用，可能有助于在轻度 FD 中检测早期器官受累。
