title: Isolated sulfite oxidase deficiency: review of two cases in one family.
abstract: OBJECTIVE
  The authors describe two cases of isolated sulfite oxidase deficiency found in one family. This is a rare autosomal-recessive disorder presenting at birth with seizures, severe neurologic disease, and ectopia lentis. It can be easily missed with metabolic screening; however, the finding of lens subluxation stresses the importance of ophthalmic assessment in making the diagnosis.
  
  
  METHODS
  Two observational case reports.
  
  
  METHODS
  Ophthalmic assessment, biochemical assay for specific urinary and plasma metabolites, magnetic resonance imaging, and gene sequencing were used to make the diagnosis of the disease in the proband. The diagnosis was subsequently recognized in a previously affected sibling after the postmortem neuropathology was reviewed. Mutation analysis was performed on cultured fibroblasts from the proband to identify and categorize the specific mutation responsible for the disease in the family. From this, future prenatal detection of sulfite oxidase deficiency is possible.
  
  
  METHODS
  The diagnosis of sulfite oxidase deficiency was established in this family, enabling appropriate genetic counseling and recurrence risk estimation.
  
  
  RESULTS
  Point mutations were found in both alleles of the sulfite oxidase gene in the proband. The first is a 623C-->A mutation, which predicts an A208D substitution, and the second is a 1109C-->A, which predicts an S370Y substitution. Both residues A208D and S370Y are critical for sulfite oxidase activity.
  
  
  CONCLUSIONS
  Isolated sulfite oxidase deficiency is a rare heritable disease for which mutation analysis can allow accurate prenatal screening. It often is difficult to diagnose by clinical presentation alone, but the critical finding of lens subluxation accompanying seizures and diffuse neurologic disease in an infant should alert the physician to the diagnosis.
authors.affiliation: Department of Ophthalmology, University of Alberta, Edmonton, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Edwards
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.forename: B
authors.initials: B
authors.lastname: Marriage
authors.forename: T N
authors.initials: TN
authors.lastname: Graf
authors.forename: K E
authors.initials: KE
authors.lastname: Coyne
authors.forename: K V
authors.initials: KV
authors.lastname: Rajagopalan
authors.forename: I M
authors.initials: IM
authors.lastname: MacDonald
mesh_terms: D000483:Alleles; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005190:Family; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D007906:Lens Subluxation / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D009422:Nervous System Diseases / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency* / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D012640:Seizures / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics
chemical_list: D050862:Oxidoreductases Acting on Sulfur Group Donors