Isolated Sulfite Oxidase Deficiency: A Case Report With a Novel Mutation and Review of the Literature

Abstract

Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. Plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. Mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. Seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. Ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. Plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency.

Early Features in Neuroimaging of Two Siblings With Molybdenum Cofactor Deficiency

“…Agenesis or hypoplasia of the corpus callosum was described in 5 (type A: 1; type unknown: 4) of 12 cases of MoCoD in Turkey 18 as well as in infants with ISOD 19 and was also seen in both infants in this report. Dysgenesis of the corpus callosum has a heterogeneous etiology and may be associated with metabolic disorders of organic acids, such as propionic acidemia or pyruvate dehydrogenase complex deficiency.…”

Sulfite-oxidizing enzymes

“…These severe neurological symptoms result from either point mutations in the SO protein itself (so-called isolated SO deficiency, in which only SO activity is affected), or the inability to properly produce the pyranopterindithiolate cofactor, which results in deficiencies in all Mo-containing enzymes (so-called Mo cofactor deficiency) [10][11][12]. The development of methods to clone and express human SO has revealed several different clinical point mutations that result in isolated SO deficiency [13][14][15][16]. The X-ray structure of the human SO is not yet available, although the structure of the human SO heme domain was reported [17].…”

Molybdenum Cofactor Deficiency: A New HPLC Method for Fast Quantification of S-Sulfocysteine in Urine and Serum

“…Affected patients exhibit severe neurological abnormalities, such as microcephaly, seizures, and usually die in early childhood (Johnson and Duran 2001). Sulfite oxidase deficiency (SOD) is less frequent but clinically similar to MoCD, which renders sulfite oxidase as the most important Moco enzyme in humans (Tan et al 2005). Sulfite oxidase catalyzes the oxidation of sulfite, which is generated throughout the catabolism of sulfur-containing amino acids, to sulfate (Griffith 1987;Johnson and Duran 2001).…”