We evaluated whether substrate reduction therapy with miglustat could alter the course of action myoclonus–renal failure syndrome (AMRF), a rare, progressive myoclonic epilepsy with early mortality caused by scavenger receptor class B member 2 (SCARB2) gene mutations.

We identified an AMRF patient with a biallelic combination of SCARB2 mutations determined by whole exome sequencing. SCARB2 encodes a protein that traffics β-glucocerebrosidase to the lysosomal membrane. Mutations lead to a complex pattern of glucosylceramide accumulation and neurologic symptoms including progressive action myoclonus, seizures, and ataxia. We then evaluated the effect of inhibiting glucosylceramide synthesis, as is used in Gaucher disease. The patient was treated for 3 years with miglustat after several years of steady worsening.

Progression of myoclonus halted, dysphagia resolved, some skills were reacquired, and seizures remained well controlled.

The response suggests that neurologic symptoms of SCARB2-associated AMRF could be ameliorated, at least partly, by targeting glycosphingolipid metabolism with available medications.

我们评估了使用 miglustat 进行底物减少治疗是否可以改变肌阵挛肾功能衰竭综合征 (AMRF) 的作用过程，这是一种罕见的进行性肌阵挛性癫痫，由清道夫受体 B 类成员 2 (S CARB2 ) 基因突变引起早期死亡。

我们确定了一名 AMRF 患者，该患者具有由全外显子组测序确定的SCARB2突变的双等位基因组合。SCARB2编码一种将 β-葡萄糖脑苷脂酶转运至溶酶体膜的蛋白质。突变导致葡萄糖神经酰胺积累和神经系统症状的复杂模式，包括进行性动作性肌阵挛、癫痫发作和共济失调。然后，我们评估了抑制葡糖神经酰胺合成的效果，正如在戈谢病中使用的那样。经过几年的稳定恶化后，该患者接受了 3 年的米格鲁他治疗。

肌阵挛的进展停止，吞咽困难得到解决，一些技能被重新获得，癫痫发作得到很好的控制。

该反应表明，SCARB2相关 AMRF 的神经系统症状可以通过使用现有药物靶向糖鞘脂代谢至少部分得到改善。