Aspartoacylase deficiency initially presents generally around the age of three months. Typical features include lethargy, listlessness, weak cry and suck, a lack of head control when the baby is pulled from a lying to a sitting position, hypotonia, poor visual tracking or blindness, vomiting, and seizures. Some authors have also described poor feeding, irritability, and visual inattention.
Macrocephaly, or enlarged head size, becomes prominent by the age of three to six months. After that, hypotonia progresses to spasticity, hyperreflexia, extensor plantar responses, and tonic extensor spasms. The extensor spasms may occur in response to noise.
By the age of six months, neurologic irregularities are invariably present with little or no subsequent motor development.
Blindness due to optic atrophy occurs around the age of 6 to 18 months. Seizures, usually generalized tonic-clonic ones, are noted in about 50% of patients. Unlike most leukodystrophies, the cerebrospinal fluid protein is usually within the reference range.
Pseudobulbar signs and decerebrate posturing dominate the end stage of Canavan disease. Feeding is a major issue, with prominent swallowing dysfunction and gastroesophageal reflux.
Variant Forms
The presence of variant forms of aspartoacylase deficiency is controversial. A suggested juvenile-onset form, beginning after age five, is less common. Patients with this form of the disease will have slightly delayed speech and motor skill development since childhood. It is common for such delays to go under-recognized due to their mild and nonspecific nature. Onset in adults usually resembles multiple sclerosis on clinical grounds.