Background: Isolated sulfite oxidase deficiency (ISOD) is the rarest types of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. ISOD is extremely rare and only 29 mutations have been identified and reported worldwide. Germline mutation in SUOX gene causes ISOD. Results: Here, we investigated a 5-days old Chinese girl, presented with intermittent tremor or seizures of limbs, neonatal encephalopathy, subarachnoid cyst and haemorrhage, dysplasia of corpus callosum, neonatal convulsion, respiratory failure, cardiac failure, hyperlactatemia, severe metabolic acidosis, hyperglycemia, hyperkalemia, moderate anemia, atrioventricular block and complete right bundle branch block. Karyotype and chromosomal microarray analysis were performed and identified no chromosomal abnormalities in the proband. Whole exome sequencing was performed for the proband. Sanger sequencing was performed for the proband and her family members. Whole exome sequencing identified a novel heterozygous deletion (c.1406_1421delCCTGGCAGGTGGCTAA) and a previously reported heterozygous substitution (c.1200C>G) in exon 6 of the SUOX gene in the proband. The novel heterozygous deletion leads to frameshift (p.Thr469Serfs*20) which results into the formation of a truncated sulfite oxidase of 488 amino acids. The substitution leads to a premature stop codon (p.Tyr400*) followed by the formation of a truncated sulfite oxidase of 399 amino acids. Hence, both the variants are loss-of-function variants. The proband’s father and mother is carrying the substitution and deletion in a heterozygous state respectively. These two variants were not identified in the elder brother of the proband as well as in the 100 healthy individuals. Conclusion: Here, we reported the first variant of SUOX gene associated ISOD in Chinese population. Our study not only expand the mutational spectrum of SUOX gene associated ISOD, but also strongly suggested the application of whole exome sequencing for identifying the novel disease-causing mutation in candidate genes.

Background: Dementia is a rapid growing global health challenge, and early screening in the preclinical stage is necessary. Mild cognitive impairment (MCI) is considered a transitional stage preceding dementia, and current diagnostic markers for AD are limited by cost and invasiveness. Neuropsychological tests (such as MMSE, MoCA) are valid but neither simple nor efficient enough to serve as large-scale dementia screening tools. Eye-tracking data can be encoded as cognitive activity and states, which provides quantitative and multi-dimensional attributes of cognitive function. Its application to cognitive assessment has shown promise in identifying patients with MCI or dementia. Immersive environments of virtual reality technology guarantee the integrity of eye-tracking data and the portability of VR headset enables efficient large-scale early screening of cognitive impairment in communities. Objective: Develop a 5-minute dementia screening tool — VR Eye Movement Cognitive Assessment to help physicians detect cognitive impairment as an alternative approach of traditional paper-based instruments. Methods: 201 subjects from Shenzhen Baoan Chronic Hospital were administered MoCA and VR eye movement cognitive assessments. Raw gaze data was captured by eye tracker of the VR headset and filtered as eye movements which would be encoded as features. Machine learning models were established as the predictor of MoCA score and the classifier of cognitive impairment of three education-based groups within which optimal cut-off score was given. Results: Support vector regression was proposed as the VR-AI model and achieved high correlation of 0.9 with MoCA score, greater than baseline model of 0.58. Optimal cut-off scores (less than 6 years of education: 14/15; 6 to 9 years of education: 18/19; more than 9 years of education: 23/24) can well distinguish normal and cognitively impaired subjects — with overall sensitivity of 88.5% and specificity of 83%. Conclusion: VR eye movement cognitive assessment is a portable, efficient, and quantitative dementia screening tool, which can be used for early screening of mild cognitive impairment and dementia.