当前位置: X-MOL 学术BBA Mol. Basis Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Incidental finding of cornea verticillata or lamellar inclusions in kidney biopsy: measurement of lyso-Gb3 in plasma defines between Fabry disease and drug-induced phospholipidosis
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ( IF 6.2 ) Pub Date : 2020-10-03 , DOI: 10.1016/j.bbadis.2020.165985
J. Politei , J. Frabasil , C. Durand , S. Di Pietrantonio , A. Fernandez , V. Albertón , D. Velasquez Rivas , R. Barriales-Villa , J. Larrañaga-Moreira , A.B. Schenone

Introduction

Therapy with cationic amphiphilic drugs (Amiodarone or hydroxychloroquine) may result in biochemically and ultrastructurally similar lipid inclusions in many cells also affected by Fabry disease (FD). In addition, it often results in similar clinical manifestations such as cornea verticillata. This may lead to a FD misdiagnosis, especially when a complete medical history is not available to the ophthalmologist confronted with cornea verticillata or to the pathologist examining a kidney biopsy. When enzymatic/genetic test or pathological studies are not conclusive, a specific biomarker may help clarify this dilemma. The plasma globotriaosylsphingosine (lyso-Gb3) assay has high sensitivity and specificity and is elevated above normal levels in FD.

Materials and methods

We measured plasma lyso-Gb3 levels in male patients receiving Amiodarone or hydroxychloroquine and compared it with male patients with classic and late onset variant of FD.

Results

In all Fabry patients (classic and late onset variant) α-GalA activity was deficient in dried blood spot and plasma lyso-Gb3 was above normal levels. Patients on treatment with Amiodarone or hydroxychloroquine had normal values for α-GalA activity and lyso-Gb3 in plasma.

Conclusions

Even when Amiodarone or hydroxychloroquine may decrease α-GalA activity in vitro or in cell culture, our results showed that in all patients lyso-Gb3 plasma levels remain normal with no evidence of reduction in α-GalA activity, confirming the specificity of this biomarker for the diagnosis of FD.



中文翻译:

在肾脏活检中偶然发现角膜黄斑或片状内含物:血浆中溶血性Gb3的测定定义了法布里氏病和药物诱导的磷脂中毒之间的关系

介绍

阳离子两亲药物(胺碘酮或羟氯喹)的治疗可能会在许多也受到法布里病(FD)影响的细胞中产生生物化学和超微结构相似的脂质包裹体。此外,它通常会导致类似的临床表现,例如角膜网纹。这可能会导致FD误诊,特别是当面对角膜黄斑病的眼科医生或检查肾脏活检的病理学家没有完整的病史时。当酶/基因测试或病理学研究不是结论性的时,特定的生物标志物可能有助于澄清这一难题。血浆globotriaosylsphingosine(lyso-Gb3)测定具有很高的灵敏度和特异性,并且在FD中升高到正常水平以上。

材料和方法

我们测量了接受胺碘酮或羟氯喹的男性患者的血浆溶血Gb3水平,并将其与患有FD的经典和晚期发作变异的男性患者进行了比较。

结果

在所有Fabry患者(经典和晚期发作患者)中,α-GalA活性缺乏干血斑,血浆溶血Gb3高于正常水平。接受胺碘酮或羟氯喹治疗的患者血浆中α-GalA活性和溶血性Gb3值正常。

结论

即使胺碘酮或羟氯喹可能会在体外或细胞培养中降低α-GalA活性,我们的结果也表明,所有患者中的溶血Gb3血浆水平均保持正常,而没有证据表明α-GalA活性降低,这证实了该生物标记物的特异性FD的诊断。

更新日期:2020-10-11
down
wechat
bug