ISCA2

Clinical Characteristics

Neurologic findings

  • Neurodevelopmental regression to a vegetative state
  • Cognitive disability
  • Spasticity
  • Hyperreflexia
  • Absent speech
  • Leukodystrophy of the subcortical region, cerebellum,
  • Progressive loss of developmental milestones, typically beginning during early infancy (three to seven months)
  • Spasticity
  • Impaired speech

Muscle

  • Hypotonia
  • Atrophic fibers seen on biopsy
  • Some abnormal aggregation of mitochondria

Ophthalmologic features

  • Optic atrophy
  • Loss of eye contact
  • Nystagmus
  • Visual impairment

Brain MRI findings

  • Diffuse bilateral symmetric signal abnormality in cerebral white matter
  • In some cases, signal abnormalities in the corpus callosum, internal capsule, midbrain, middle cerebellar peduncles, and cervical spinal cord

Supportive laboratory findings

  • – Increased CSF glycine, glutamate, and lactate
  • – Fibroblasts show decreased mitochondrial complex I and II activity
  • – Mildly decreased complex IV activity
  • – Decreased mtDNA levels
  • – Decreased mitochondrial membrane potential
  • – Decreased oxidative phosphorylation and ATP production
  • Respiratory chain enzyme analysis on muscle tissue reveals deficient activity of complex II and IV