Sulfite oxidase deficiency

Deficiency or Toxicity in Humans. Molybdenum deficiency in humans results in deranged metaboHsm of sulfur and purines and symptoms of mental disturbances (130). Toxic levels produce elevated uric acid in blood, gout, anemia, and growth depression. Faulty utiH2ation results in sulfite oxidase deficiency, a lethal inborn error. 

Sulfite oxidase deficiency (+Mo-cofactor) u Sulfocysp, Taup... 

Homocyst(e)ine CBS deficiency Cobalamin defects/defi-ciency MTHFR deficiency Methionine adenosyltrans-ferase deficiency Hyperhomocysteinemia Sulfite oxidase deficiency... 

Taurine Sulfite oxidase deficiency Mo-cofactor deficiency Hemolytic plasma ... 

Johnson JL, Duran M (2001) Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, NY, pp 3163-3177... 

Sulfite oxidase concentrations vary in animals and humans, and the efficiency of sulfite oxidation depends primarily on sulfite oxidase activity (Gunnison and Palmes 1974). Cohen et al. (1973) observed sulfite oxidase activity to be lower in the livers of young versus mature rats, sulfite oxidase activity in 1-d-old rats was one-tenth that of adults. Decreased activity of sulfite oxidase in sulfite-oxidase-deficient rats resulted in higher in vivo concentrations of sulfite, whereas sulfite-oxidase-competent rats exposed to sulfur dioxide lacked sulfite in the plasma (Gunnison et al. 1987). 

Gunnison, A.F., A.Sellakumar, D.Currie, and E.A.Snyder. 1987. Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase-deficient rats. J. Toxicol. Environ. Health 21(1—2) 141—... 

A very small number of children have been reported who are unable to synthesize molybdopterin they show severe neurological abnormalities shordy after birth and fail to survive more than a few days. As expected from the metabolic roles of molybdopterin, they have low blood concentrations of uric acid and sulfate, and abnormally high levels of xanthine and sulfite. The neurological damage is probably caused by sulfite, because similar abnormalities are seen in children with isolated sulfite oxidase deficiency (Reiss, 2000). 

Kisker, C., Schindelin, H., Pacheco, A., Wehbi, W. A., Garrett, R. M., Rajagopalan, K. V., Enemark, J. H., and Rees, D. C., 1997 Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase Cell 91 9733983. 

Garrett, R. M., Johnson, J. M., Graf, T. N., Feigenbaum, A., and Rajagopalan, K.V., 1998, Human sulfite oxidase R160Q identification of the mutation in a sulfite oxidase-deficient patient and expression and characterization of the mutant enzyme, Proc. Natl. Acad. Sci. (USA) 95 6394116398. 

This family includes the sulfite oxidases and dehydrogenases of prokaryotes Thiobacilli sp.), plants, birds, and animals, and the assimilatory nitrate reductases from bacteria, algae, fungi, and plants. The sulfite oxidases of higher eukaryotes are 100-110kDa homodimers (Table 1) they are located in the mitochrondrial intermembrane space and catalyze the oxidation of toxic sulfite to innocuous sulfate (equation 7). Human sulfite oxidase deficiency leads to major neurological abnormalities, mental retardation, dislocation of the ocular lenses, and early death. ... 

Hereditary sulfite oxidase deficiency can occur alone or with xanthine oxidase deficiency. Both enzymes contain molybdenum (Chapter 27). Patients with sulfite oxidase deficiency exhibit mental retardation, major motor seizures, cerebral atrophy, and lens dislocation. Dietary deficiency of molybdenum (Chapter 37) can cause deficient activity of sulfite and xanthine oxidases. 

Environmental exposure to PAHs can also occur along with exposure to other environmental pollutants. The effects of exposure to SO2 (either by inhalation or systemically with endogenous sulfite/bisulfite anions that accumulated as a result of induced sulfite oxidase deficiency) on benzo[a]pyrene-induced lung tumors were studied in male Sprague-Dawley rats (Gunnison et al. 

Moco is essential for the activity of sulfite oxidase, XDH, and AO, the three molybdoenzymes present in humans. Human Moco deficiency leads to the pleiotropic loss of all three of these molybdoenzymes and usually progresses to death at an early age. In humans, a combined deficiency of sulfite oxidase and XDH was first described by Duran et al To date, more than 100 cases of Moco deficiency or isolated sulfite oxidase deficiency are known worldwide. Isolated sulfite oxidase deficiency is a related disease in which molybdenum cofactor biosynthesis is normal, but sulfite oxidase activity is altered. The clinical symptoms of Moco deficiency are indistinguishable from those of isolated sulfite oxidase deficiency with a notable exception that xanthinuria is absent in the latter. In both cases, affected neonates show feeding difficulties, neurological abnormalities such as attenuated brain growth, untreatable seizures, dislocated ocular lenses in most cases, and death in early childhood. Although milder symptoms are occasionally observed, none of the treatments tested... 

J. L. Johnson M. Duran, Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. C. R. Scriver A. L. Beaudet W. S. Sly D. Valle B. Childs B. Vogelstein, Eds. McGraw-Hill New York, 2001 pp 3163-3177. 

The production of transgenic and knockout animals represents a powerful molecular biology technique whereby spontaneous inborn errors of metabolism (e.g., sulfite oxidase deficiency) have provided extensive and valuable insight into the identification of essential elements, for example molybdenum (O Dell and Sunde 1997). 

Molybdenum cofactor deficiency (MoCoD) is an autosomal recessive, fatal neurological disorder, characterized by the combined deficiency of sulphite oxidase, xanthine dehydrogenase, and aldehyde oxidase. No therapy is known for this rare disease, which results in neonatal seizures and other neurological symptoms identical to sulfite oxidase deficiency. Heterozygous carriers of a MoCo deficiency allele do not display any symptoms (Reiss et al. 1999). 

A nutritional molybdenum deficiency with clinical symptoms similar to those of sulfite oxidase deficiency was identified in a human patient receiving long-term total parenteral nutrition (TPN) (Abumurad et al. 1981). The clinical symptoms included irritability leading to coma, tachycardia, tachypnea, and night blindness. A reduced intake of protein and sulfur-amino acids alleviated the symptoms, but they were aggravated by infusion of sulfite. The biochemical findings were low tissue sulfite oxidase activity a 25-fold increase in thiosulfate excretion a 70% reduction in urinary output of sulfate and a marked rise in plasma methionine. The clinical symptoms of molybdenum deficiency were totally eliminated by daily supplementation of 300 pg of the element. 

An inborn defect of metabolism that is closely related to sulfite oxidase deficiency and is more prevalent in the human population is that of molybdenum cofactor deficiency (Johnson 1997). In this disease syndrome, the activities of all molybdenum enzymes are affected owing to a lack of functional molybdopterin. The absence of sulfite oxidase is clearly most devastating. A number of individuals have been identified with xanthinuria (specific loss of XHD), and the resultant clinical symptoms are generally mild (Simmonds et al. 1995). A smaller class of patients has more recently been described with deficiencies in XHD and aldehyde oxidase, with mild clinical symptoms (Reiter et al. 1990). 

Until now, no therapy has been available for either form of sulfite oxidase deficiency. Prenatal diagnosis is possible by assay of sulfite oxidase activity in cultured amnio-cytes or directly in chorionic villus biopsy material (Johnson et al. 1991). 

Iereverre F, Mudd SH, Heizer WD and Faster L (1967) Sulfite oxidase deficiency studies of a patient with mental retardation, dislocated ocular lenses, and abnormal urinary excretion of S-sulfo-L-cys-teine, sulfite, and thiosulfate. Bioebem Med 1 187 -217. 

Johnson JL, Jones HP and Rajagopaian KV (1977) In vitro reconstitution of demolybdosulfite oxidase by a molybdenum cofactor from rat liver and other sources. J Biol Chem 252 4994-5003. Johnson JL and Rajagopaian KV (1976) Human sulfite oxidase deficiency. Characterization of the molecular defect in a multicomponent system. J Clin Invest 58 551-556. 

Mudd SH, Ieeeveeee F and Faster L (1967) Sulfite oxidase deficiency in man demonstration of the enzymatic defect. Science 156 1599—1602. 

Inborn errors of metabolism. Sulfite oxidase deficiency is a rare disorder resulting from the accumulation of cysteine-5-sulfate (CSS) (Mudd et al., 1967). This leads to neuronal degeneration that is manifest clinically as blindness and spastic quad-riplegia. Death typically occurs early in infancy. CSS is a structural analogue of Glu that displays excitotoxic activity when systemically administered to infant rats or when injected into the brains of adult rats (Olney et al., 1975). CSS toxicity is blocked by NMDA antagonists. 

Olney, J.W., Misra, C.H. and DeGubareff, T. (1975). Cyste-ine-5-sulfate a brain damaging metabolite in sulfite oxidase deficiency. 7. Neuropathol. Exp. Neurol. 34 167-176. 

Preparations for the treatment of miscellaneous disorders of amino acid metabolism are available for sulfite oxidase deficiency, hyperlysinemia and nonketotic hyperglycinemia (Table 41.11). There are formulas suitable for the first year of life. At a minimal daily amino acid requirement of 3 g amino acid per kg bodyweight, a newborn term infant of average birth weight of 3.5 kg, and the infant at 1 year would have an iodine intake of 38 pg/day and 108 pg/day, respectively. 

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