Neurodegenerative diseases of childhood have different forms of presentation and it can be clinically challenging to identify regression. In the early stages, it is usually very difficult to establish the progressive nature of disease, as the time course may be very slow. Other more common pathologies in pediatrics can produce a similar picture and must first be excluded.

In general, following a transient stage of normality or with a previous history of delayed psychomotor development, obvious motor, cognitive, or global deterioration can be observed. Seizures and dementia are considered characteristic features of gray matter involvement, while spasticity and ataxia indicate white matter involvement. Progressive dementia, seizures, ataxia, tone and motor disorders, sensory defects, retinal alterations, and even extra-neurological manifestations may coexist.

The final diagnosis is based on clinical symptoms, including careful assessment of family and clinical history and detailed neurological examination. Frequently, complementary tests such as neuroimaging and genetic testing are needed.