Isolated sulfite oxidase deficiency - Review of two cases in one family

Objective: The authors describe two cases of isolated sulfite oxidase defic iency found in one family. This is a rare autosomal-recessive disorder pres enting at birth with seizures, severe neurologic disease, and ectopia lenti s. It can be easily missed with metabolic screening; however, the finding o f lens subluxation stresses the importance of ophthalmic assessment in maki ng the diagnosis. Design: Two observational case reports. Intervention/Methods: Ophthalmic assessment, biochemical assay for specific urinary and plasma metabolites, magnetic resonance imaging, and gene seque ncing were used to make the diagnosis of the disease in the proband. The di agnosis 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 sp ecific mutation responsible for the disease in the family. From this, futur e prenatal detection of sulfite oxidase deficiency is possible. Main Outcome Measures: The diagnosis of sulfite oxidase deficiency was esta blished in this family, enabling appropriate genetic counseling and recurre nce 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 S370 Y substitution. Both residues A208D and S370Y are critical for sulfite oxid ase activity. Conclusions isolated sulfite oxidase deficiency is a rare heritable disease for which mutation analysis can allow accurate prenatal screening. It ofte n is difficult to diagnose by clinical presentation alone, but the critical finding of lens subluxation accompanying seizures and diffuse neurologic d isease in an infant should alert the physician to the diagnosis.