eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Sulfite Oxidase Deficiency

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
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Updated: Feb 18, 2009

Introduction

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 Media file 1). 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 Media file 2). 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.

Clinical

History

• Pregnancy and delivery history are typically normal, although numerous infants with sulfite oxidase deficiency have had depressed Apgar scores.
• The "classic presentation" includes intractable seizures in the first days or weeks of life and abnormal tone (particularly opithistonus). Feeding difficulties are common shortly after birth. Most individuals have profound mental retardation.
• Later or milder presentations of sulfite oxidase deficiency are being reported with increasing frequency. These presentations include neurologic regression with loss of previously acquired milestones or movement disorders. A review of 22 cases of isolated sulfite oxidase deficiency noted that age of onset was after the first month of life in 9 cases (10 wk to 15 mo) and that the oldest onset cases were more likely to have mild or no developmental delays; in some cases, movement or tone abnormalities were presenting symptoms instead of seizures.¹

Physical

• Birth weight, height, and head circumference are usually normal in individuals with sulfite oxidase deficiency. Microcephaly may develop in infancy.
• Neurologic examination may note the following:
  • Axial hypotonia with peripheral hypertonia
  • Intractable tonic/clonic seizures
  • Myoclonus
  • Opisthotonus
  • Movement disorder
  • Hyperekplexia
• The following characteristic craniofacial anomalies may be observed (see Media file 3):
  • Narrow bifrontal diameter
  • Deep-set eyes
• The following ocular abnormalities are also common:
  • Dislocated lenses (may develop after the neonatal period)
  • Lack of response to light

Causes

• Both isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are autosomal recessive traits. Two complementation groups are involved in molybdenum cofactor synthesis.
• Animal studies have found that elevated sulfite levels have neurotoxic effects in rats.

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