Clinical features: macrocephaly, poor head control, lack of psychomotor development, spasticity, optic atrophy, seizures. Symptom onset before age 4 months in >50%. Children eventually become decerebrate, die of intercurrent illness, may survive into third decade.

CT and MRI: increased lucency of white matter, poor demarcation of gray and white matter; later, severe brain atrophy with enlarged CSF spaces.

Pathology: (a) intramyelin vacuolation (spongy degeneration) initially of deep layers of cortex, eventually diffuse; (b) giant abnormal mitochondria in superficial layers of white matter.

Diagnosis: deficiency of aspartoacylase in skin fibroblasts. Gene on chromosome 17p.

Other conditions associated with spongy degeneration of brain: intoxication by triethyltin or hexachlorophene, some neonatal acidurias, some mitochondrial disorders, Aicardi-Goutières syndrome, vanishing white matter disease.

Clinical features: symptom onset age 6–18 months with arrest of motor development, then loss of skills. Tone increased or decreased. Ataxia, nystagmus, optic atrophy, dementia common; seizures rare. Death usually by age 10.

Pathology: axonal spheroids (eosinophilic, argyrophilic, ovoid inclusions that distend axons and myelin sheaths) in brain, spinal cord, peripheral nerves. Severe cerebellar atrophy, spongy degeneration of basal ganglia.

Diagnosis: laboratory tests not helpful. Nerve, muscle, rectal, or conjunctival biopsy confirmatory when spheroids found in nerves or NMJ, but false negative results possible. Definite diagnosis at autopsy.

Treatment: symptomatic.