Neuronopathic

Neuronopathic is an adjective used in neurology and medical genetics to describe diseases or phenotypes in which neurons bear the primary burden of pathology. In neuronopathic disorders, the central nervous system and/or peripheral nervous system are directly affected by the disease process, often with early or prominent neurological symptoms; by contrast, non-neuronopathic forms may spare the CNS and display systemic or visceral involvement as the dominant feature.

The term is commonly applied to lysosomal storage diseases and other neurometabolic or neurodegenerative conditions with neuronal involvement. Examples include Gaucher disease types 2 and 3 (neuronopathic), Niemann-Pick disease type A and type C, GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases), Sanfilippo syndrome (MPS III), Krabbe disease, and certain forms of mucopolysaccharidoses. Neuronopathic involvement can also be described in broader neuronal ceroid lipofuscinoses and other inherited or acquired disorders where neurons are preferentially affected.

Clinical features of neuronopathic disorders are variable but often include developmental delay or regression, seizures, hypotonia or hypertonia, ataxia, dystonia or other movement disorders, cognitive decline, and progressive motor impairment. Onset can range from infancy to adolescence, with progression influenced by the specific disease. Pathophysiology typically involves accumulation or toxicity within neurons, leading to dysfunction and cell loss, sometimes with neuroinflammation and secondary white matter changes.

Diagnosis relies on a combination of clinical assessment, genetic testing, and, when appropriate, enzyme activity assays or biomarker studies. Neuroimaging may show cerebral atrophy or white matter abnormalities. Management is usually supportive and multidisciplinary; disease-specific therapies such as enzyme replacement or substrate reduction may be limited by CNS delivery, though CNS-directed therapies and gene therapies are active areas of research. Prognosis varies widely by disease and onset.