Sulfite Oxidase Deficiency Workup

  • Author: Georgianne L Arnold, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 1, 2012
 

Laboratory Studies

A positive sulfite dipstick finding of very fresh urine is highly suggestive of sulfite oxidase deficiency; however, a negative dipstick finding should not eliminate suspicion.

For quantitative plasma and urine amino acids, alert the laboratory to look for characteristic cysteine metabolite s-sulfocysteine, which may not be detected or reported unless specifically requested. S-sulfocysteine elutes in the early part of the chromatogram, before the main amino acids of interest do. Special techniques may be required to differentiate the peak from other more common substances.

Urine organic acids may reveal lactate (a nonspecific finding) but should rule out common organic acidemias. Urinary urothion (a degradation product of molybdopterin) can be measured by a few laboratories. A low level is virtually diagnostic for molybdenum cofactor deficiency (except in cases of profound molybdenum deficiency). Urinary thiosulfate (a metabolite of cysteine) can also be measured in a few selected laboratories.

An elevated urinary thiosulfate level is essentially diagnostic of sulfite oxidase deficiency or molybdenum cofactor deficiency. The plasma uric acid level is typically low or low-normal in individuals with molybdenum cofactor deficiency; however, it is normal in those with isolated sulfite oxidase deficiency. Plasma lactate and pyruvate levels may be highly elevated, although this finding is nonspecific. Urinary xanthine and hypoxanthine levels can be measured in selected laboratories. These levels are elevated in individuals with molybdenum cofactor deficiency but are normal in those with sulfite oxidase deficiency.

Mutations in the SUOX gene (sulfite oxidase) and in the component of the molybendum cofactor (MOCS1, MOCS2, or GEPH) have been described, with no single predominate mutation.

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Imaging Studies

Cranial CT or MRI may reveal the following:

  • Abnormal gyration
  • Cerebral atrophy
  • Decreased density of white matter
  • Dilated ventricles
  • Neuronal loss
  • Cystic lesions (in basal ganglia and/or cerebellum)
  • Calcifications
  • Cerebral edema

Magnetic resonance spectroscopy (MRS) findings in 3 cases revealed a reduced peak area N -acetylaspartate–to–total creatine ratio, an increased peak choline–to–total creatine ratio, increased lactate and lipid levels, and pronounced elevation of glutamate and glutamine levels.[4]

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Other Tests

Prenatal diagnosis has been achieved by measurement of sulfite oxidase activity in chorionic villi or by DNA analysis in families in whom the mutation is known in the index case.

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Histologic Findings

Neuropathological findings include cerebral atrophy or edema; microgyri and abnormal sulci; multicystic subcortical and juxtacortical focal lesions in white matter; microscopic lesions in frontal, temporal, and occipital cortex; demyelination; spongiosis; and microcavitation.

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Contributor Information and Disclosures
Author

Georgianne L Arnold, MD  Faculty, Department of Pediatrics, Divison of Genetics, University of Pittsburgh School of Medicine

Georgianne L Arnold, MD is a member of the following medical societies: American College of Medical Genetics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, and Society for the Study of Inborn Errors of Metabolism

Disclosure: Biomarin Grant/research funds clinical trial

Specialty Editor Board

Christian J Renner, MD  Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina School of Medicine; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Johnson-Winters K, Tollin G, Enemark JH. Elucidating the catalytic mechanism of sulfite oxidizing enzymes using structural, spectroscopic, and kinetic analyses. Biochemistry. Aug 31 2010;49(34):7242-54. [Medline]. [Full Text].

  2. Tan WH, Eichler FS, Hoda S, et al. Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature. Pediatrics. Sep 2005;116(3):757-66. [Medline].

  3. Bindu PS, Christopher R, Mahadevan A, Bharath RD. Clinical and imaging observations in isolated sulfite oxidase deficiency. J Child Neurol. Aug 2011;26(8):1036-40. [Medline].

  4. Hoffmann C, Ben-Zeev B, Anikster Y, et al. Magnetic resonance imaging and magnetic resonance spectroscopy in isolated sulfite oxidase deficiency. J Child Neurol. Oct 2007;22(10):1214-21. [Medline].

  5. Arnold GL, Greene CL, Stout JP, Goodman SI. Molybdenum cofactor deficiency. J Pediatr. Oct 1993;123(4):595-8. [Medline].

  6. Johnson JL. Prenatal diagnosis of molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. Prenat Diagn. Jan 2003;23(1):6-8. [Medline].

  7. Johnson JL, Wadman SK. Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. In: The Metabolic and Molecular Bases of Inherited Disease. 2nd ed. 1995:2271-86.

  8. Kucukatay V, Savcioglu F, Hacioglu G, et al. Effect of sulfite on cognitive functions in normal and sulfite oxidase deficient rats. Neurotoxicol Teratol. 2005;27:47-54. [Medline].

  9. Simmonds HA, Hoffmann GF, Perignon JL, et al. Diagnosis of molybdenum cofactor deficiency. Lancet. Feb 20 1999;353(9153):675. [Medline].

  10. Waring WS, Maxwell S. Diagnosis of molybdenum cofactor deficiency. Lancet. Feb 20 1999;353(9153):675-6. [Medline].

 
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Molybdenum cofactor deficiency.
Sulfite oxidase deficiency and molybdenum cofactor deficiency in the metabolism of sulfated amino acids.
Pictured is an infant with sulfite oxidase deficiency. Note the narrow bifrontal diameter and deep-set eyes.
 
 
 
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