Alternative titles; symbols
SNOMEDCT: 367368009; ICD10CM: E72.19; ORPHA: 833, 99731; DO: 0111270;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.2 | Sulfite oxidase deficiency | 272300 | Autosomal recessive | 3 | SUOX | 606887 |
A number sign (#) is used with this entry because isolated sulfite oxidase deficiency (ISOD) is caused by homozygous or compound heterozygous mutation in the sulfite oxidase gene (SUOX; 606887) on chromosome 12q13.
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, who 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 who had 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.
Bender et al. (2019) reported a boy, born of consanguineous Turkish parents, who presented on the third day of life with hypopnea and seizures. He had mild metabolic acidosis and elevated creatine kinase. Brain MRI showed globally and severely impaired diffusion, white matter hyperintensity, and cerebellar hypoplasia. He developed dyskinetic movements, spasticity, and frequent vomiting in addition to continued seizures. EEG slowed diffuse slowing of activity and epileptic discharges. MRI at 3 months of age showed severe brain atrophy with multicystic leukoencephalopathy, epidural and subdural hygromas, and large infratentorial cerebrospinal fluid spaces. Biochemical findings in the patient at 3.5 months of age included a positive urine sulfite test, elevated urine S-sulfocysteine, normal levels of urine xanthine oxidase biomarkers, and low urothione. Another MRI at 5 months of age showed progressive brain atrophy and microcephaly; however, the brainstem was relatively spared and showed signs of myelination. At 4.5 years of age, the patient had severely impaired intellectual development with no speech or vocalizations, and he was unable to sit independently. He had seizures resembling myoclonic fits and dyskinesia.
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.
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.
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.
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.
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.
By direct sequencing of the SUOX gene in a Turkish boy, born of consanguineous parents, with ISOD, Bender et al. (2019) identified a homozygous missense mutation (G362S; 606887.0006). Sulfite oxidase activity was absent in patient fibroblasts. G362S mutant apo-SUOX protein expressed in HEK293 cells had reduced stability and reduced efficiency of molybdenum cofactor incorporation compared to wildtype, which provided evidence for a protein maturation defect. Patient fibroblasts treated with molybdate-containing growth media showed increased SUOX activity, suggesting that dietary treatment with molybdenum should be considered as a potential treatment in patients with ISOD and a mutation causing a protein maturation defect.
Administration of tungsten to rats produces sulfite oxidase deficiency (Dulak et al., 1984).
Barbot, C., Martins, E., Vilarinho, L., Dorche, C., Cardoso, M. L. A mild form of infantile isolated sulphite oxidase deficiency. Neuropediatrics 26: 322-324, 1995. [PubMed: 8719749] [Full Text: https://doi.org/10.1055/s-2007-979783]
Bender, D., Kaczmarek, A. T., Santamaria-Araujo, J. A., Stueve, B., Waltz, S., Bartsch, D., Kurian, L., Cirak, S., Schwarz, G. Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. Hum. Molec. Genet. 28: 2885-2899, 2019. [PubMed: 31127934] [Full Text: https://doi.org/10.1093/hmg/ddz109]
Dulak, L., Chiang, G., Gunnison, A. F. A sulphite oxidase-deficient rat model: reproductive toxicology of sulphite in the female. Food Chem. Toxicol. 22: 599-607, 1984. [PubMed: 6540737] [Full Text: https://doi.org/10.1016/0278-6915(84)90268-0]
Garrett, R. M., Johnson, J. L., Graf, T. N., Feigenbaum, A., Rajagopalan, K. V. Human sulfite oxidase R160Q: identification of the mutation in a sulfite oxidase-deficient patient and expression and characterization of the mutant enzyme. Proc. Nat. Acad. Sci. 95: 6394-6398, 1998. [PubMed: 9600976] [Full Text: https://doi.org/10.1073/pnas.95.11.6394]
Irreverre, F., Mudd, S. H., Heizer, W. D., Laster, L. Sulfite oxidase deficiency: studies of a patient with mental retardation, dislocated ocular lenses, and abnormal urinary excretion of S-sulfo-L-cysteine, sulfite and thiosulfate. Biochem. Med. 1: 187-199, 1967.
Johnson, J. L., Rajagopalan, K. V. Human sulfite oxidase deficiency: characterization of the molecular defect in a multicomponent system. J. Clin. Invest. 58: 551-556, 1976. [PubMed: 956384] [Full Text: https://doi.org/10.1172/JCI108500]
Kang, A. H., Trelstad, R. L. A collagen defect in homocystinuria. J. Clin. Invest. 52: 2571-2578, 1973. [PubMed: 4729050] [Full Text: https://doi.org/10.1172/JCI107449]
Kisker, C., Schindelin, H., Pacheco, A., Wehbi, W. A., Garrett, R. M., Rajagopalan, K. V., Enemark, J. H., Rees, D. C. Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase. Cell 91: 973-983, 1997. [PubMed: 9428520] [Full Text: https://doi.org/10.1016/s0092-8674(00)80488-2]
Mudd, S. H., Irreverre, F., Laster, L. Sulfite oxidase deficiency in man: demonstration of the enzymatic defect. Science 156: 1599-1602, 1967. [PubMed: 6025118] [Full Text: https://doi.org/10.1126/science.156.3782.1599]
Seidahmed, M. Z., Alyamani, E. A., Rashed, M. S., Saadallah, A. A., Abdelbasit, O. B., Shaheed, M. M., Rasheed, A., Hamid, F. A., Sabry, M. A. Total truncation of the molybdopterin/dimerization domains of SUOX protein in an Arab family with isolated sulfite oxidase deficiency. Am. J. Med. Genet. 136A: 205-209, 2005. [PubMed: 15952210] [Full Text: https://doi.org/10.1002/ajmg.a.30796]
Shih, V. E., Abroms, I. F., Johnson, J. L., Carney, M., Mandell, R., Robb, R. M., Cloherty, J. P., Rajagopalan, K. V. Sulfite oxidase deficiency: biochemical and clinical investigations of a hereditary metabolic disorder in sulfur metabolism. New Eng. J. Med. 297: 1022-1028, 1977. [PubMed: 302914] [Full Text: https://doi.org/10.1056/NEJM197711102971902]
Shih, V. E., Carney, M. M., Mandell, R. A simple screening test for sulfite oxidase deficiency: detection of urinary thiosulfate by a modification of Sorbo's method. Clin. Chim. Acta 95: 143-145, 1979. [PubMed: 509724] [Full Text: https://doi.org/10.1016/0009-8981(79)90348-6]
Streeten, B. W. The nature of the ocular zonule. Trans. Am. Ophthal. Soc. 80: 823-854, 1982. [PubMed: 6763807]
Touati, G., Rusthoven, E., Depondt, E., Dorche, C., Duran, M., Heron, B., Rabier, D., Russo, M., Saudubray, J. M. Dietary therapy in two patients with a mild form of sulphite oxidase deficiency: evidence for clinical and biological improvement. J. Inherit. Metab. Dis. 23: 45-53, 2000. [PubMed: 10682307] [Full Text: https://doi.org/10.1023/a:1005646813492]
van der Klei-van Moorsel, J. M., Smit, L. M. E., Brockstedt, M., Jakobs, C., Dorche, C., Duran, M. Infantile isolated sulphite oxidase deficiency: report of a case with negative sulphite test and normal sulphate excretion. Europ. J. Pediat. 150: 196-197, 1991. [PubMed: 2044591] [Full Text: https://doi.org/10.1007/BF01963565]
Vianey-Liaud, C., Desjacques, P., Gaulme, J., Dorche, C., Vanlieferinghen, P., Dechelotte, P., Divry, P. A new case of isolated sulphite oxidase deficiency with rapid fatal outcome. J. Inherit. Metab. Dis. 11: 425-426, 1988. [PubMed: 3149702] [Full Text: https://doi.org/10.1007/BF01800433]
Wadman, S. K., Cats, B. P., de Bree, P. K. Sulfite oxidase deficiency and the detection of urinary sulfite. (Letter) Europ. J. Pediat. 141: 62-63, 1983.