Infantile spasms and hyperekplexia associated with isolated sulfite oxidase deficiency

JAMA Neurol. 2014 Jun;71(6):782-4. doi: 10.1001/jamaneurol.2013.5083.


Importance: Isolated sulfite oxidase deficiency (ISOD) causes severe intellectual disability, epilepsy, and shortened life expectancy. Intractable seizures are invariable in children with ISOD; however, to our knowledge, infantile spasms with a corresponding hypsarrhythmia pattern on electroencephalogram have never been reported. In addition, the nonepileptic paroxysmal movement disorder hyperekplexia has not previously been reported with ISOD.

Observations: We describe an infant with ISOD who initially presented with neonatal seizures, diffusion restriction noted on magnetic resonance imaging, and elevated serum S-sulfocysteine consistent with ISOD. A homozygous mutation in the SUOX gene was identified, confirming the diagnosis. Uniquely, this patient developed a profound accentuated startle response that did not have a corresponding electrographic change on electroencephalogram consistent with hyperekplexia. This was followed by a change in the child's electroencephalogram to the chaotic pattern of hypsarrhythmia and brief tonic seizures with attenuation of the hypsarrhythmia pattern characteristic of infantile spasms.

Conclusions and relevance: The evolution of seizures associated with ISOD is poorly characterized because of the small number of patients. We report what we believe to be the first case of a child with ISOD who developed infantile spasms and hyperekplexia. This expands the phenotypes associated with ISOD and also should caution clinicians to not assume that all abnormal movements are seizures.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Amino Acid Metabolism, Inborn Errors / genetics*
  • Electroencephalography / methods
  • Humans
  • Infant, Newborn
  • Magnetic Resonance Imaging / methods
  • Male
  • Mutation / genetics*
  • Oxidoreductases Acting on Sulfur Group Donors / genetics*
  • Seizures / etiology
  • Seizures / genetics*
  • Spasms, Infantile / etiology
  • Spasms, Infantile / genetics*
  • Stiff-Person Syndrome / etiology
  • Stiff-Person Syndrome / genetics*
  • Sulfite Oxidase / deficiency*
  • Sulfite Oxidase / genetics


  • Oxidoreductases Acting on Sulfur Group Donors
  • SUOX protein, human
  • Sulfite Oxidase

Supplementary concepts

  • Sulfite oxidase deficiency