Encephalopathy due to sulfite oxidase deficiency

Encephalopathy due to sulfite oxidase deficiency, also known as isolated sulfite oxidase deficiency (ISOD), is an extremely rare autosomal recessive metabolic disorder caused by mutations in the SUOX gene, which encodes the enzyme sulfite oxidase. This enzyme is essential for the final step in the degradation of sulfur-containing amino acids (methionine and cysteine), converting toxic sulfite to sulfate. When the enzyme is deficient, sulfite and S-sulfocysteine accumulate in the body, leading to severe neurological damage. The condition primarily affects the central nervous system and the eyes. The disease most commonly presents in the neonatal period with intractable seizures, feeding difficulties, and progressive encephalopathy. Affected infants typically develop severe intellectual disability, microcephaly, and spasticity. A characteristic finding is lens subluxation (ectopia lentis), which may develop in the first months or years of life. Brain imaging often reveals progressive cerebral atrophy, white matter changes, and cystic degeneration resembling hypoxic-ischemic encephalopathy. A milder, late-onset form has been described in rare cases, presenting with movement abnormalities and less severe cognitive impairment. Diagnosis is supported by elevated urinary sulfite, S-sulfocysteine, and thiosulfate levels, along with low plasma cystine and homocysteine. Confirmatory testing involves measuring sulfite oxidase enzyme activity in fibroblasts or identifying biallelic pathogenic variants in the SUOX gene. It is important to distinguish this condition from molybdenum cofactor deficiency, which presents similarly but involves deficiency of multiple molybdenum-dependent enzymes. Currently, there is no curative treatment. Management is primarily supportive, including seizure control, nutritional support, and physical therapy. Dietary restriction of methionine and cysteine has been attempted with limited success. The prognosis for the severe neonatal form is generally poor, with significant morbidity and early mortality.

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