Miglustat Therapy for SCARB2 -Associated Action Myoclonus-Renal Failure Syndrome.

Objective: 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 (S CARB2 ) gene mutations.

Methods: 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.

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

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