Investigation of MTHFR and thrombophilia-related gene mutations andbiochemical parameters in cases diagnosed with PANS

Objective: The relationship between the immune system and neuropsychiatric disorders has attracted attention in recent years. PANDAS, characterised by sudden-onset obsessive-compulsive disorder and tics following streptococcal infections in childhood, has been defined, and the broader concept of PANS has emerged. This study investigated the frequency of MTHFR C677T, MTHFR A1298C, Factor V Leiden, and Prothrombin G20210A mutations in children diagnosed with PANS and their relationship with psychiatric symptoms, clinical severity, and biochemical parameters. Keywords: PANS, PANDAS, MTHFR, Factor V Leiden, Prothrombin G20210A, Thrombophilia. Methods: The study included 40 children aged 6–18 years diagnosed with PANS and 60 healthy controls. Participants completed a sociodemographic data form, the C-YBOKÖ, YGTSS, and K-SADS-PL; laboratory investigations included mutation analyses, ASO, vitamin B12, folate, vitamin D, TSH, and complete blood count parameters. Results: Age and gender were similar in the PANS and control groups. The mean age at first onset in the PANS group was 8.15±2.49 years. Premature and caesarean delivery were more common, and maternal and paternal education levels were high. The number of upper respiratory tract infections, tonsillectomy, penicillin prophylaxis, and allergic disease were more common in the PANS group. Psychiatric diagnoses were generally have comorbidity (72.5%). Folate level was low in PANS (p=0.017) and vitamin B12 level was low in the control group (p=0.011); vitamin D, ASO, and TSH levels did not differ. There were no differences between groups in terms of MTHFRC677T, MTHFRA1298C, FIIG20210A, and FVG1691A mutations, but the MTHFRA1298C mutation was associated with tic severity in the PANS group (motor tic p=0.013, vocal tic p=0.014, total tic p=0.023). Conclusion: These findings suggest that genetic predisposition and autoimmune processes may play a role together in the pathogenesis of PANS. MTHFR polymorphisms may affect both biochemical parameters and the clinical aspects. Studies with larger samples are recommended.