Sulfite Oxidase Deficiency

Abstract

Study of a 4 1/2-year-old boy with the unusual combination of acute infantile hemiplegia, ectopia lentis and the absence of homocystinuria showed large amounts of abnormal sulfur-containing metabolites (sulfite, thiosulfate and S-sulfocysteine) in the urine. Sulfite and S-sulfocysteine were also present in the plasma. His inorganic sulfate excretion was only 50 per cent of total sulfur, as compared with 75 to 95 per cent by controls. Loading with L-cysteine hydrochloride and L-methionine further increased the excretion of sulfite and thiosulfate, but not inorganic sulfate excretion. Sulfite oxidase activity in skin fibroblasts average 1.07 nmol of cytochrome d reduced per milligram of protein per minute in control lines; it was not detectable (less than 5 per cent) in the patient. Activity was reduced in both parents (0.50 in the father and 0.32 in the mother)--compatible with autosomal recessive inheritance. Good biochemical responses to a low sulfur amino acid diet suggest that early treatment may benefit the patient.

Protein Radical Formation Resulting from Eosinophil Peroxidase-catalyzed Oxidation of Sulfite

“…In fact, in humans, the loss of sulfite oxidase is fatal in infancy or early childhood (52). It is noteworthy that in cases of sulfite oxidase deficiency, the concentration of sulfite in plasma is abnormal (10 M to ϳ2 mM) (5,53). The capacity of sulfite oxidase for sulfite oxidation is normally extremely high (54 -56); the reaction proceeds via a one-step, two-electron oxidation to sulfate with no free radical intermediates (7).…”

“…Bisulfite is used when not referring to a particular sulfite species. Sulfite is generated endogenously during the normal metabolic processing of sulfur-containing amino acids (5). Sulfite is toxic to the lung and can cause allergic reactions in humans, especially in sulfite-hypersensitive individuals, most commonly causing bronchoconstriction in asthmatics (6).…”

Inborn errors of molybdenum metabolism: combined deficiencies of sulfite oxidase and xanthine dehydrogenase in a patient lacking the molybdenum cofactor.

“…Fibroblasts were cultured from punch skin biopsy materials as described (21). Cells were lysed for analysis by sonication in 5 vol of 10 mM potassium phosphate buffer, pH 7.8.…”

“…The lysates were centrifuged at 20,000 X g for 10 min. Samples of the supernatant fractions were used directly for radioimmunoassay or subjected to gel filtration for sulfite oxidase activity assay (21). The diagnosis of sulfite oxidase deficiency plus xanthine dehydrogenase deficiency was first suspected after the finding of abnormal metabolites during a multi-chromatographic screening of the patient's urine.…”

Simultaneous occurrence of xanthine oxidase and sulfite oxidase deficiency. A molybdenum dependent inborn error of metabolism?

“…The excretory pattern of sulfur-compounds in our patient is characteristic of SO deficiency• The following cysteine metabolites, expressed in mmoles/g creatinine, were found to be elevated in the urine: sulfite, up to 6 (normal: not present) ; S-sulfocysteine: 2.3-2. 6 (normal: not present); taurine: 1.9-7.6 (normal 1.2 mmoles/day) and thiosulfate: 0.80 (normal: 0.02 mmoles/1). Urinary sulfate was decreased (1.9-13-7 mmoles/g creatinine) SSrbo and 0hman '4 have established a sulfate-thiosulfate ratio amounting to 1000 in urines of healthy adults.…”