Clinical, neuroimaging, and genetic analysis of isolated sulfite oxidase deficiency in Chinese neonates: A case series and literature review

Background : Currently, no curative treatment is available for infantile sulfite oxidase deficiency (ISOD), and disease progression is primarily managed by restricting sulfur-containing amino acids in the diet. Furthermore, despite its overall rarity, the prevalence of ISOD has demonstrated an upward trend in the Chinese population in recent years. Accordingly, this study investigated the clinical phenotype, imaging characteristics, mutation spectrum, and prognosis of ISOD in Chinese newborns. Methods : We retrospectively analyzed the clinical data from seven neonates with genetically confirmed ISOD from southeastern China between November 2018 and March 2025. The collected data included maternal and infant factors, clinical manifestations, laboratory results, and neuroimaging and genetic findings. The study cohort was further expanded through a systematic review of 13 additional neonatal ISOD cases reported in the Chinese and international literature, resulting in a combined cohort comprising 20 patients. Results : All infants (100%) presented with intractable seizures within the first few days of life. Other common clinical presentations included increased muscle tone (75%) and feeding difficulty (70%). Lens dislocation was uncommon in this neonatal cohort (5%). Abnormalities in cranial imaging—primarily presenting as symmetric abnormal signals in both cerebral hemispheres and basal ganglia—were observed in all cases, which could be misdiagnosed as hypoxic-ischemic encephalopathy. Laboratory tests revealed elevated urinary sulfite levels or decreased plasma homocysteine levels in some cases. Genetic analysis identified 11 distinct pathogenic variants of the SUOX gene, with c.1200C>G (p.Tyr400Ter) being the most common hotspot mutation in China. The prognosis was extremely poor; only five patients (25%) survived following symptomatic treatment, including sulfur-restricted diets, with a median follow-up of 10 months (range: 6–22 months). All surviving infants exhibited refractory epilepsy and severe developmental delays. Conclusion : The hallmark features of ISOD in Chinese neonates include refractory seizures occurring shortly after birth and characteristic neuroimaging patterns. The c.1200C>G (p.Tyr400Ter) mutation in the SUOX gene is the most common pathogenic variant in this population. Given the extremely poor prognosis and lack of effective treatment, prenatal genetic diagnosis is recommended to enable early intervention in high-risk families.