NGS-Based Genetic Approach to Identify Rare Lysosomal Storage Disorders in Patients With Neurological Manifestations

LYSO-NEXT uses genetic sequencing to identify undiagnosed lysosomal storage disorders in adults with unexplained neurological symptoms. Participants undergo whole-exome sequencing, which examines the protein-coding regions of DNA. A small subgroup with inconclusive results and strong clinical suspicion undergoes additional long-read sequencing to detect genetic changes that may be missed by the initial test. The study assesses the proportion of participants diagnosed with a lysosomal storage disorder and the diagnostic yield of each sequencing approach.

Inclusion Criteria: * Signed informed consent for participation in the study. * Age 18 years or older. * Neurological manifestations without an established genetic diagnosis: early-onset parkinsonism, ataxia, motor neuropathy, myopathy, intellectual disability, epilepsy, young-onset stroke, or chronic pain syndromes with childhood onset. Exclusion Criteria: \- Neurological signs and symptoms definitively attributable to acquired causes, including trauma, tumors, infections, or acquired metabolic conditions.