The disease is clinically heterogeneous. The progression is slower in the late-onset forms and patients may survive for as much as 20 years after the disease has started. After a period of normal development, gait disturbances develop, usually by 2 years of age. Initial examination shows distal weakness of the feet with loss of ankle reflexes. Progressive weakness of all limbs results in generalized hypotonia and hyporeflexia.
Cerebral demyelination follows, causing dementia, spasticity, and blindness.
In juvenile MLD, the onset of symptoms is usually between 5 and 10 years, but may be delayed until adolescence or occur as early as late infancy. Despite this overlap with the infantile form, they differ in terms of clinical manifestations. In the juvenile form, no symptoms of peripheral neuropathy occur, progression is slow, and the protein content of the CSF may be normal. Mental regression, speech disturbances, and clumsiness of gait are the prominent initial features. Dementia usually progresses slowly over a period of 3 to 5 years, but may sometimes progress rapidly to a vegetative state.