Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Neuronopathic Gaucher disease (GBA1-PD) exhibits diverse clinical presentations.
• Traditional classification into types I and II often fails to capture the full phenotypic spectrum.
• A continuum of phenotypes complicates diagnosis and management.

Purpose of the Study:

• To characterize an intermediate phenotype of neuronopathic Gaucher disease.
• To describe the clinical and genotypic features of affected children.
• To improve understanding of Gaucher disease heterogeneity.

Main Methods:

• Retrospective case series analysis.
• Clinical data collection including neurological assessments and seizure history.
• Genotypic analysis to identify mutations in the GBA1 gene.

Main Results:

• Nine children presented with a delayed onset but rapidly progressive neurological phenotype.
• Key features included refractory seizures and oculomotor abnormalities.
• Genotypic heterogeneity was observed among the patients, indicating diverse underlying mutations.

Conclusions:

• An intermediate phenotype of neuronopathic Gaucher disease exists, characterized by specific neurological manifestations.
• This phenotype presents challenges in traditional disease categorization.
• Understanding genotypic heterogeneity is crucial for comprehensive Gaucher disease management.