1. Background

• a genetic defect affecting aspartoacylase (normally cleaves the N-acetyl group from N-acetylaspartic acid) -> accumulation of N-acetylaspartic acid throughout the white matter (specifically in astrocytes)

1. Spongy Vacuolization/Degeneration

• accumulation of N-acetylaspartic acid leads to vacuolization of the white matter with astrocyte swelling -> spongy degener-ation of myelin fibres
• required for definite diagnosis but not pathognomonic as spongy vacuolization is seen in other disorders, i.e., Maple Syrup
• Urine Disease, Phenylketonuria

1. Type I - Neonatal Form

• onset: at birth
• death within the first few weeks of life
  1. Neurological Manifestations

  • hypotonia, lethargy, decreased spontaneous movements
  • difficulty sucking, swallowing, and feeding
  • irritability
  • Cheyne-Stokes respiration

2. Type II - Infantile Form

• onset: first few months of life
• most common form
• death by 3-4 years of age
  1. Neurologic Manifestations

  1. Initial

  • plateauing then delayed psychomotor development
  • infantile hypotonia, lethargy, poor head & neck con-trol

  2. Later

  1. Movement Disorders

  hypotonia -> spasticity with decorticate and de- cerebrate posturing

  choreoathetosis

  2. Others

  megencephaly +/- increased ICP

  seizures

  nystagmus, optic atrophy, and blindness

  failure to thrive with gastroesophageal reflux

3. Type III - Juvenile Form

• onset: over 5 years of age
• death in adolescence
  1. Neurological Manifestations

  1. Initial

  • ataxia, tremor, mental deterioration, ptosis

  2. Later

  • dementia, dysarthria, progressive cerebellar syndrome spasticity
  • optic atrophy, abnormal retinal pigmentation

1. Diagnosis

• abnormal amounts of N-acetylaspartic acid in urine (300x normal), blood, and CSF (urine and serum for amino acids)
• deficiency of aspartoacylase (less than 40% of normal) in cul-tured skin fibroblasts

2. Imaging Studies