COMPLEMENTATION IN VARIANTS OF SULFITE OXIDASE DEFICIENCY

Abstract

Hereditary disorders causing a deficiency of sulfite oxidase (SO) activity result in the accumulation of sulfite, sulfocysteine and thiosulfate and a clinical syndrome of seizures, developmental delay, and ectopia lentis. The defect may be in the structural enzyme protein (apoenzyme) of SO or due to the absence of its active molybdenum (Mo) cofactor, in which case Mo-dependent xanthine oxidase activity is also reduced. Study of fibroblast lines of one patient (A) with SO apoenzyme defect and 5 unrelated patients (B-F) with Mo cofactor deficiency revealed no detectable SO activity in any case. Complementation tests showed that SO activity was restored when Line B was cocultured with each of 5 other lines. No activity was detected in other pairwise combinations. Complementation occurred without heterokaryon formation, suggesting that the corrective factor may be a diffusible precursor of the cofactor. These findings confirm heterogeneity of SO deficiency; at least 3 variants can be distinguished. Line A has a mutation of the structural gene for SO apoenzyme which may have affected the binding of the heme or Mo cofactor but is without effect on its antigenicity. Among the cofactor deficient lines, Line B clearly has a defect different from and correctable by the other 4 lines. These 4 could have a common defect or non-complementing lesions in the biosynthetic pathway of the cofactor.

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