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.

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. 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. 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. 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.

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