Lekárska genetika a diagnostika 1/2024

Neurodegeneration and lysosomal storage disorders

Lysosomal storage disorders (LSDs) constitute a heterogeneous group of inherited metabolic disorders with a broad spectrum of clinical manifestations. On one hand, there are patients with severe organ involvement, and on the other hand, asymptomatic carriers of a pathological variant of a specific gene. Increased awareness of LSDs, the availability of diagnostic methods, and new therapeutic options have led to a growing trend of newly diagnosed LSD patients worldwide, including Slovakia. A common and relentless feature of most LSDs is the onset and progression of neurodegenerative symptoms leading to premature death. Interestingly, advanced studies using specific neuronal models for each disorder have revealed common pathological mechanisms between LSDs and adult neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and others. Importantly, these new insights may bring innovative therapeutic approaches for both of these disease groups, potentially reversing their devastating impact on patients, families, and society as a whole.

Keywords: lysosomal storage disorders, neurodegeneration, sphingolipids, sphingolipidosis, neurodegenerative disorders, treatment