RARE DISEASE
Isolated sulfite oxidase deficiency
Isolated sulfite oxidase deficiency
Isolated sulfite oxidase deficiency
Synonyms: ISOD, Sulfocysteinuria
Synonyms: ISOD, Sulfocysteinuria
Synonyms: ISOD, Sulfocysteinuria
Drug discovery
0
drugs
With orphan designations
Overview
Isolated sulfite oxidase deficiency (ISOD) is a rare, autosomal recessive neurometabolic disorder caused by SUOX gene mutations, impairing sulfite-to-sulfate conversion. This results in toxic sulfite accumulation, leading to severe neurological manifestations such as refractory seizures, encephalopathy, spasticity, and progressive brain damage. Diagnosis relies on elevated urinary sulfocysteine, low plasma cystine, and characteristic MRI findings (cystic white matter lesions, basal ganglia abnormalities). No cure exists; management focuses on supportive care and dietary modifications, though prognosis remains poor, particularly in neonatal-onset cases [1][2][5][13].
Therapies
Low-protein diets restricting methionine/cysteine (≤150 mg/kg/day) show biochemical improvement but limited clinical impact [1][3][4].
Antiepileptic drugs (e.g., vigabatrin) for seizure control; gastrostomy for feeding support [2][13].
Experimental approaches include thiamine, cysteamine, and precursor Z (for MoCo deficiency), though efficacy remains unproven [2][4][13].
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare ophthalmic disorders
Research Papers
67 drug discovery papers about Isolated sulfite oxidase deficiency, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
67 drug discovery papers about Isolated sulfite oxidase deficiency, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-05 | A flexible synthetic diet platform for Drosophila nutrigenomics.
Nutrient-gene interactions are key determinants of metabolic disease phenotypes, but systematic analysis remains constrained by the labour required to generate precisely defined diets. To address this, we developed a flexible method for assembling synthetic diets for Drosophila melanogaster from individual stock solutions, enabling rapid and controlled modification of dietary composition. Using this approach, we generated a rational array of 51 diets in which single nutrients were varied systematically. We first showed that diets prepared using the flexible method performed comparably to standard preparation methods in wild-type flies, with similar developmental timing, survival, adult body weight, and starvation resistance. As a proof-of-concept, we then applied this dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe metabolic disorder caused by defective sulfur amino acid catabolism. This validated previously identified nutrient-specific effects, including survival and pupariation rescue by cysteine depletion, while also revealing additional amino acid-modified diets that improved pupal survival. This platform provides a scalable and versatile in vivo framework for systematically interrogating genotype-specific nutritional responses in Drosophila. It should facilitate the identification of diet-gene interactions relevant to metabolic disease and support broader nutritional screening across disease models.
2026-03-03 | A flexible diet platform for the nutrigenomic screening of Drosophila disease models
Abstract Nutrient-gene interactions shape metabolic disease phenotypes, but systematic testing is limited by the effort required to produce defined diets. We developed a flexible protocol that assembles precisely defined synthetic diets for Drosophila melanogaster from individual stock solutions. Using this approach, we generated a rational array of 51 single-nutrient-varied diets and demonstrated that flexible and standard preparation methods produce comparable developmental timing, survival, adult body weight, and starvation resistance in wildtype flies. Applying the dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe condition caused by impaired sulfur amino acid catabolism, revealed nutrient-specific effects on pupal survival and pupariation timing, including rescue by cysteine depletion and other amino acid modified diets. This platform provides a scalable in vivo framework for mapping genotype-specific nutritional responses across Drosophila disease models. Key points Developed a flexible platform for assembling precisely defined synthetic diets in Drosophila . Generated a rational 51-diet array, enabling scalable nutrigenomic screening. Flexible and standard diet preparations yielded matching developmental and adult fitness outcomes. Dietary array screening in a sulfite oxidase deficiency model recapitulated cysteine sensitivity and identified novel nutrient modifiers.
2025-09-25 | In vitro investigation of caspase-3 dependent and independent apoptotic processes in cortical and hippocampal neurons triggered by S-sulfocysteine-induced cell death
Purpose: S-sulfocysteine (SSC), a toxic byproduct of sulfur-containing amino acid metabolism, accumulates in conditions such as molybdenum cofactor deficiency (MoCD) and isolated sulfite oxidase deficiency (iSOD), leading to severe neurodegeneration. Despite evidence of SSC's neurotoxicity, the apoptotic mechanisms it triggers remain unclear, particularly in different brain regions. This study aimed to investigate the region-specific apoptotic pathways induced by SSC in hippocampal HT-22 and primary cortical neurons, focusing on caspase-dependent and -independent mechanisms. Materials and methods: Neuronal cells were treated with increasing doses of SSC, and cell viability, glutathione (GSH) levels, and apoptosis-related proteins (AIF, calpain, cytochrome c, caspase-3) were assessed using CCK-8 assay, GSH enzymatic assay, and ELISA. The protective effects of specific inhibitors targeting AIF, calpain, and cytochrome c were also evaluated. Results: SSC reduced cell viability in both neuronal types with half-maximal lethal dose (LD50) values of 150 μM (HT-22) and 155 μM (cortical neurons). In both models, SSC elevated AIF and calpain levels, whereas cytochrome c and caspase-3 were significantly increased only in cortical neurons. GSH levels initially rose at 2–8 hours and declined by 16 hours. Inhibitors of AIF, calpain, and cytochrome c partially restored viability, with combined administration offering the most robust protection. Conclusion: SSC induces both caspase-independent and caspase-dependent apoptosis in a region-specific manner: HT-22 cells predominantly activate AIF and calpain, while cortical neurons engage additional cytochrome c and caspase-3 pathways. These findings suggest distinct molecular vulnerabilities and offer potential targets for therapeutic intervention in sulfite-related neurodegenerative diseases.
2025-05-29 | Kaplan-Meier estimated survival rates for individuals with ISOD.
Median survival of individuals within the study sample was 60 months (N = 72). Black line indicates the estimated survival curve. Dashed lines illustrate the 95% confidence interval of estimated survival. Censored individuals, who were alive and lost to follow-up, are marked with a “+” at last reported age. ISOD; isolated sulfite oxidase deficiency.
2025-05-29 | Study flow diagram: Identification of clinical case reports with ISOD.
The reports analyzed were published up to 31 October 2023. ISOD, isolated sulfite oxidase deficiency. (JPG)
small molecules
2026-06-05 | A flexible synthetic diet platform for Drosophila nutrigenomics.
Nutrient-gene interactions are key determinants of metabolic disease phenotypes, but systematic analysis remains constrained by the labour required to generate precisely defined diets. To address this, we developed a flexible method for assembling synthetic diets for Drosophila melanogaster from individual stock solutions, enabling rapid and controlled modification of dietary composition. Using this approach, we generated a rational array of 51 diets in which single nutrients were varied systematically. We first showed that diets prepared using the flexible method performed comparably to standard preparation methods in wild-type flies, with similar developmental timing, survival, adult body weight, and starvation resistance. As a proof-of-concept, we then applied this dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe metabolic disorder caused by defective sulfur amino acid catabolism. This validated previously identified nutrient-specific effects, including survival and pupariation rescue by cysteine depletion, while also revealing additional amino acid-modified diets that improved pupal survival. This platform provides a scalable and versatile in vivo framework for systematically interrogating genotype-specific nutritional responses in Drosophila. It should facilitate the identification of diet-gene interactions relevant to metabolic disease and support broader nutritional screening across disease models.
2026-03-03 | A flexible diet platform for the nutrigenomic screening of Drosophila disease models
Abstract Nutrient-gene interactions shape metabolic disease phenotypes, but systematic testing is limited by the effort required to produce defined diets. We developed a flexible protocol that assembles precisely defined synthetic diets for Drosophila melanogaster from individual stock solutions. Using this approach, we generated a rational array of 51 single-nutrient-varied diets and demonstrated that flexible and standard preparation methods produce comparable developmental timing, survival, adult body weight, and starvation resistance in wildtype flies. Applying the dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe condition caused by impaired sulfur amino acid catabolism, revealed nutrient-specific effects on pupal survival and pupariation timing, including rescue by cysteine depletion and other amino acid modified diets. This platform provides a scalable in vivo framework for mapping genotype-specific nutritional responses across Drosophila disease models. Key points Developed a flexible platform for assembling precisely defined synthetic diets in Drosophila . Generated a rational 51-diet array, enabling scalable nutrigenomic screening. Flexible and standard diet preparations yielded matching developmental and adult fitness outcomes. Dietary array screening in a sulfite oxidase deficiency model recapitulated cysteine sensitivity and identified novel nutrient modifiers.
2025-09-25 | In vitro investigation of caspase-3 dependent and independent apoptotic processes in cortical and hippocampal neurons triggered by S-sulfocysteine-induced cell death
Purpose: S-sulfocysteine (SSC), a toxic byproduct of sulfur-containing amino acid metabolism, accumulates in conditions such as molybdenum cofactor deficiency (MoCD) and isolated sulfite oxidase deficiency (iSOD), leading to severe neurodegeneration. Despite evidence of SSC's neurotoxicity, the apoptotic mechanisms it triggers remain unclear, particularly in different brain regions. This study aimed to investigate the region-specific apoptotic pathways induced by SSC in hippocampal HT-22 and primary cortical neurons, focusing on caspase-dependent and -independent mechanisms. Materials and methods: Neuronal cells were treated with increasing doses of SSC, and cell viability, glutathione (GSH) levels, and apoptosis-related proteins (AIF, calpain, cytochrome c, caspase-3) were assessed using CCK-8 assay, GSH enzymatic assay, and ELISA. The protective effects of specific inhibitors targeting AIF, calpain, and cytochrome c were also evaluated. Results: SSC reduced cell viability in both neuronal types with half-maximal lethal dose (LD50) values of 150 μM (HT-22) and 155 μM (cortical neurons). In both models, SSC elevated AIF and calpain levels, whereas cytochrome c and caspase-3 were significantly increased only in cortical neurons. GSH levels initially rose at 2–8 hours and declined by 16 hours. Inhibitors of AIF, calpain, and cytochrome c partially restored viability, with combined administration offering the most robust protection. Conclusion: SSC induces both caspase-independent and caspase-dependent apoptosis in a region-specific manner: HT-22 cells predominantly activate AIF and calpain, while cortical neurons engage additional cytochrome c and caspase-3 pathways. These findings suggest distinct molecular vulnerabilities and offer potential targets for therapeutic intervention in sulfite-related neurodegenerative diseases.
2025-05-29 | Kaplan-Meier estimated survival rates for individuals with ISOD.
Median survival of individuals within the study sample was 60 months (N = 72). Black line indicates the estimated survival curve. Dashed lines illustrate the 95% confidence interval of estimated survival. Censored individuals, who were alive and lost to follow-up, are marked with a “+” at last reported age. ISOD; isolated sulfite oxidase deficiency.
2025-05-29 | Study flow diagram: Identification of clinical case reports with ISOD.
The reports analyzed were published up to 31 October 2023. ISOD, isolated sulfite oxidase deficiency. (JPG)
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