# Case Report: Progressive myoclonus epilepsy as an early manifestation of neuronopathic Gaucher disease

## TL;DR

A 20-year-old man with progressive myoclonus epilepsy was diagnosed with neuronopathic Gaucher disease, highlighting the importance of genetic testing for early diagnosis.

## Contribution

This case report adds to the understanding of PME as an early manifestation of neuronopathic Gaucher disease and emphasizes the need for metabolic and genetic testing.

## Key findings

- The patient had two GBA1 variants consistent with neuronopathic GD type 3 despite no hepatosplenomegaly or skeletal abnormalities.
- Most GD3-PME cases showed generalized or multifocal polyspike-wave discharges and later cerebellar or brainstem atrophy.
- Recurrent compound-heterozygous GBA1 variants and poor therapeutic response were common in GD3-PME patients.

## Abstract

Gaucher disease (GD) is a lysosomal storage disorder caused by biallelic GBA1 variants. Epilepsy is uncommon in GD and rarely manifests as progressive myoclonus epilepsy (PME), making early recognition difficult. We describe a 20-year-old man with childhood-onset myoclonus that progressed to drug-resistant generalized seizures and cognitive decline. Video-electroencephalography (VEEG) showed generalized polyspike-wave discharges associated with myoclonic jerks, whereas brain magnetic resonance imaging was initially normal. Cerebrospinal fluid studies, metabolic screening, and autoimmune encephalitis antibody panels were unremarkable. Glucocerebrosidase activity was markedly reduced, and a targeted myoclonic-epilepsy gene panel identified two GBA1 variants: c.907C > A (p. Leu303Ile) and c.1505G > A (p. Arg502His), indicating a presumed compound-heterozygous state consistent with neuronopathic GD type 3. No hepatosplenomegaly or skeletal abnormalities were detected. Seizure control remained poor despite multiple antiseizure medications and vagus nerve stimulation (VNS). To contextualize this case, we systematically reviewed 22 publications encompassing 71 GD3-PME patients. Most cases presented in childhood, frequently showed typical electrophysiological patterns of generalized or multifocal polyspike-wave discharges, and had early normal MRI followed by later cerebellar or brainstem atrophy. Recurrent compound-heterozygous GBA1 variants, markedly reduced enzyme activity, and poor therapeutic response were common findings. The accompanying systematic review highlights the heterogeneity and therapeutic limitations of GD3-associated PME and underscores the importance of incorporating metabolic and genetic testing into the evaluation of unexplained PME for timely diagnosis and tailored management.