Aspartoacylase deficiency

Alternative names

Spongy degeneration of the brain; Canavan disease

Definition

Canavan disease is an inherited disorder of aspartic acid metabolism. It is characterized by degeneration of the white matter of the brain.

Causes, incidence, and risk factors

Canavan disease is inherited as an autosomal recessive trait. It is more common among Ashkenazi Jews than in the general population.

A deficient enzyme, aspartoacylase, results in the accumulation of N-acetylaspartic acid in the brain. This causes a degeneration of the white matter.

Typically, symptoms begin in the first year of life. Parents tend to notice when a child is not reaching particular developmental milestones, including poor muscle tone and lack of head control. Eventually, the child can develop feeding problems, seizures, and loss of vision.

Although death often occurs before 18 months of age, some live until they are teenagers or, rarely, young adults.

Symptoms

• A family history of Canavan disease
  
• Decreased muscle tone (hypotonia), especially of the neck muscles
  
• Abnormal posture with flexed arms and straight legs
  
• Feeding difficulties
  
• Nasal regurgitation
  
• Swallowing difficulties
  
• Reflux with vomiting
  
• Increasing head size (macrocephaly)
  
• Head lag
  
• Failure to meet milestones
  
• Seizures
  
• Severe mental retardation
  
• Blindness
  

Signs and tests

• Hyperreflexive
  
• Joint stiffness
  
• Optic atrophy
  

Tests:

• Head CT showing degeneration of white matter (leukodystrophy)
  
• Head MRI scan showing degeneration of white matter (leukodystrophy)
  
• Urine chemistry, increased N-acetylaspartic acid (increased secretion)
  
• CSF chemistry, increased N-acetylaspartic acid (increased levels)
  
• Blood chemistry, increased N-acetylaspartic acid (increased levels)