#272300
ICD+
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| SULFOCYSTEINURIA | ||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | ||||||||||||||||||||||||||||||||||||||||||||||||
| SULFITE OXIDASE DEFICIENCY | ||||||||||||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Synopsis | ||||||||||||||||||||||||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because sulfocysteinuria is caused by mutation in the sulfite oxidase gene (SUOX; 606887). | ||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Features | ||||||||||||||||||||||||||||||||||||||||||||||||
| In an infant with fatal neurologic disease and ectopia lentis, Mudd et al. (1967) found increased sulfite in the urine with markedly decreased inorganic sulfate excretion. A deficiency in the activity of sulfite oxidase, an enzyme that normally catalyzes conversion of sulfite to sulfate, was postulated. Sibs of the infant had died, probably of the same disorder. Van der Klei-van Moorsel et al. (1991) described a case of sulfite oxidase deficiency in which onset of symptoms occurred at 11 months of age. No ocular abnormalities were found. A milder form of sulfite oxidase deficiency with a late onset was reported by Barbot et al. (1995) in a 7-year-old mentally retarded Portuguese girl whose parents were first cousins. The patient had an ataxic gait, generalized dystonia and choreoathetosis, and minimal development of language. This mild form cannot be distinguished from combined molybdenum cofactor deficiency on clinical grounds. The sulfite test may appear negative and sulfate excretion may be in the normal range (van der Klei-van Moorsel et al., 1991). Garrett et al. (1998) described a 5-year-old girl born of first-cousin parents of Dutch descent. She exhibited developmental delay and hypotonia during the first 2 years of life with regression beginning at approximately 21 months of age. She had 2 healthy sibs. She had 2 seizures at approximately 5 months of age but none thereafter. At age 2 years, bilateral dislocation of the lenses was detected, and calcification of the basal ganglia and hypoplasia of the cerebellar vermis were documented on computed tomography and magnetic resonance imaging scans. Ataxia, dystonia, and choreoathetotic movements became progressively worse. She had mild eczema, fine hair, and delayed teething, but normal nails and joints. She had significant irritability and spasms needing sedation at night. At age 5 years, she had significant failure to thrive with feeding problems, aspiration, and generalized hypertonia. She was found to have a mutation resulting in an arg-to-gln substitution at amino acid 160 (606887.0001) of liver sulfite oxidase. Touati et al. (2000) reported 2 unrelated patients with isolated sulfite oxidase deficiency, with a mild clinical course and late onset of symptoms. In 1 patient, the disease started at 15 months with an acute crisis of agitation, unexplained crying, and restlessness following otitis. In the other patient, the diagnosis was made at 10 months when the patient presented with slight motor delay and dislocation of lenses. In both patients, sulfite oxidase activity in fibroblasts was undetectable. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Inheritance | ||||||||||||||||||||||||||||||||||||||||||||||||
| Sulfocysteinuria is an autosomal recessive disorder. Vianey-Liaud et al. (1988) reported an affected child of a consanguineous Algerian couple. The proband, a boy, died at 9 days of life. Two older sibs, a boy and a girl, had died in the first days of life, apparently of the same disorder. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Pathogenesis | ||||||||||||||||||||||||||||||||||||||||||||||||
| Johnson and Rajagopalan (1976) showed that the defect in this disorder is indeed in sulfite oxidase and not in the specific molybdenum (Mo) cofactor required for activation of de-molybdo sulfite oxidase. (See 252150 for a disorder of the molybdenum cofactor.) Antibody specific for sulfite oxidase showed no crossreacting material. Reviewing the nature of the ocular zonule, Streeten (1982) pointed out that the zonular fibers are composed of glycoprotein with a high concentration of cysteine, which undoubtedly explains their susceptibility to abnormal formation in diseases of sulfur metabolism. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Diagnosis | ||||||||||||||||||||||||||||||||||||||||||||||||
| Wadman et al. (1983) called attention to a simple 'strip test' for sulfite in the urine and pointed to states giving false-positive or false-negative results. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Clinical Management | ||||||||||||||||||||||||||||||||||||||||||||||||
| Shih et al. (1977) studied a 54-month-old boy with acute infantile hemiplegia and ectopia lentis. They observed a good biochemical response to a low sulfur amino acid diet. In the 2 patients reported by Touati et al. (2000), dietary therapy consisted of a diet low in protein from natural foods (daily methionine intake 130-150 mg) and a synthetic amino acid mixture (50 g per day) without cystine and methionine. A comparison of clinical and biochemical parameters was made between the period before treatment and after 2 years of treatment. Restriction in protein and sulfur amino acids brought about a dramatic decrease of urinary thiosulfate and S-sulfocysteine. It also brought about a generalized hypoaminoacidemia with a low plasma methionine and cystine in both patients. Furthermore, both patients grew normally with no signs of neurologic deterioration, and there was evidence of progress in psychomotor development. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||||||||||||||||||||||||||
| Kisker et al. (1997) characterized 4 missense mutations in the SUOX gene in cell lines from patients with isolated sulfite oxidase deficiency (606887.0001-606887.0004). Seidahmed et al. (2005) reported a male infant with isolated sulfite oxidase deficiency from a consanguineous Arab family, in whom they identified homozygosity for a 1-bp deletion in the SUOX gene (606887.0005). Seidahmed et al. (2005) stated that this was the first mutation in the SUOX gene found in an Arab family. | ||||||||||||||||||||||||||||||||||||||||||||||||
| Animal Model | ||||||||||||||||||||||||||||||||||||||||||||||||
| Administration of tungsten to rats produces sulfite oxidase deficiency (Dulak et al., 1984). | ||||||||||||||||||||||||||||||||||||||||||||||||
| See Also: | ||||||||||||||||||||||||||||||||||||||||||||||||
| Irreverre et al. (1967); Kang and Trelstad (1973); Shih et al. (1979) | ||||||||||||||||||||||||||||||||||||||||||||||||
| REFERENCES | ||||||||||||||||||||||||||||||||||||||||||||||||
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