Sulfite Oxidase Deficiency

Author: Georgianne L Arnold, MD; Chief Editor: Bruce Buehler, MD more...

Updated: Feb 18, 2009

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Background
Pathophysiology
Epidemiology
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Background

Sulfite oxidase deficiency is an inborn error of the metabolism of sulfated amino acids. Individuals affected with sulfite oxidase deficiency most commonly present in the neonatal period with intractable seizures, characteristic dysmorphic features, and profound mental retardation.

Pathophysiology

Inherited defects in the sulfite oxidase enzyme cause the phenotype of sulfite oxidase deficiency in a minority of cases. However, most cases of this disorder are associated with deficiency of the molybdenum-containing pterin cofactor (molybdenum cofactor deficiency). Molybdenum cofactor is associated with the enzymes sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase (see the image below).

Molybdenum cofactor deficiency.

Sulfite oxidase converts sulfite to sulfate. Xanthine dehydrogenase catalyzes the hydroxylation of xanthine and hypoxanthine to produce uric acid. Finally, aldehyde oxidase hydroxylates hypoxanthine into xanthine and functions in detoxification.

As sulfite oxidase deficiency and molybdenum cofactor deficiency have virtually identical phenotypes, the CNS toxicity appears to be secondary to loss of function of sulfite oxidase. Methionine and cysteine normally are metabolized to sulfite and then are oxidized to sulfate by the enzyme sulfite oxidase (see the image below).

Sulfite oxidase deficiency and molybdenum cofactor deficiency in the metabolism of sulfated amino acids.

When sulfite oxidase is deficient, alternate metabolic pathways for sulfite are augmented, including formation of metabolites s-sulfocysteine and thiosulfate. S-sulfocysteine probably substitutes for cysteine in connective tissues. This substitution appears to weaken the zonule of the lens (a tissue normally rich in cysteine) and results in the characteristic dislocated lenses. The pathogenesis of the brain damage in those with sulfite oxidase deficiency is not known but may be related to sulfite accumulation or lack of sulfate in the CNS.

Frequency

United States

Frequency of sulfite oxidase deficiency is unknown; however, this disorder is probably underdiagnosed.

International

Worldwide, approximately 50 cases of sulfite oxidase deficiency have been reported. The preponderance of reported cases in Europe and the United States most likely represents increased recognition in these countries.

Mortality/Morbidity

In most cases, this disorder is fatal in infancy or early childhood. Survivors of sulfite oxidase deficiency often have profound mental retardation. Some cases of individuals with sulfite oxidase deficiency with later presentation and more favorable outcome have been reported.

Race

Molybdenum cofactor defect and sulfite oxidase deficiency are panethnic.

Sex

Both sexes are equally affected.

Age

Traditionally, infants with this disorder were reported to present in the neonatal period. However, an increasing number of patients have been reported with later onset or deterioration after an intercurrent illness.

Proceed to Clinical Presentation

Contributor Information and Disclosures

Author

Georgianne L Arnold, MD Director of Inherited Metabolic Disorders Clinic, Department of Pediatrics and Genetics, Associate Professor, University of Rochester School of Medicine and Dentistry

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; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD Clinical Professor, Department of Pediatrics, University of South Carolina; 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

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].
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].
Arnold GL, Greene CL, Stout JP, Goodman SI. Molybdenum cofactor deficiency. J Pediatr. Oct 1993;123(4):595-8. [Medline].
Johnson JL. Prenatal diagnosis of molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. Prenat Diagn. Jan 2003;23(1):6-8. [Medline].
Johnson JL, Wadman SK. Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency. In: The Metabolic and Molecular Bases of Inherited Disease. 2^nd ed. 1995:2271-86.
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].
Simmonds HA, Hoffmann GF, Perignon JL, et al. Diagnosis of molybdenum cofactor deficiency. Lancet. Feb 20 1999;353(9153):675. [Medline].
Waring WS, Maxwell S. Diagnosis of molybdenum cofactor deficiency. Lancet. Feb 20 1999;353(9153):675-6. [Medline].