Evaluation of inflammatory markers in patients with Mucopolysaccharidosis Type 4

Aim: Mucopolysaccharidoses, or MPS, are a rare group of genetic diseases that belong to the lysosomal storage diseases (LSD) category. The illness arises from mutations that cause a decrease or absence of lysosomal enzymes that break down glycosaminoglycans (GAG). There are seven subtypes of mucopolysaccharidosis, each resulting in a build-up of GAG in lysosomes due to reduced enzyme activity from genetic mutations. While the organs affected vary depending on the subtype of mucopolysaccharidosis, the accumulation of GAG leads to progressive damage in these organs. It is widely recognized that GAG accumulation is a key factor in developing mucopolysaccharidoses. However, it is important to note that inflammation and oxidative damage resulting from the lysosomal accumulation of glycosaminoglycans also play a significant role in the manifestation of clinical symptoms. While treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation have been used to address mucopolysaccharidosis group diseases for some time, long-term follow-up has revealed that these treatments may not fully address bone-related symptoms. As a result, the potential benefits of anti-oxidative therapy in conjunction with other treatments are being explored. Available studies suggest that both the effects of GAG on oxidative stress and the use of antioxidants may be beneficial in treating MPS. Our study investigates inflammatory markers in MPS Type IV patients to better understand their role in the pathogenesis of the disease. Material and Method: We conducted a thorough examination of patients diagnosed with Mucopolysaccharidosis Type 4 at Istanbul University - Cerrahpaşa, Cerrahpaşa Faculty of Medicine's Pediatric Nutrition and Metabolism outpatient clinic. We documented patients' complaints, examination findings, blood test results, and organ involvement data. Additionally, we measured neopterin, biopterin, tryptophan, and kynurenine levels in our Pediatric Metabolism laboratory, and IL-1 beta, IL-6, TNF-alpha, IFN-gamma, Human chondroitin sulfate, and human keratan sulfate in an external center laboratory. To ensure accuracy, we included a control group of healthy volunteers with similar age and gender distribution as our patients, who did not have any diseases that could affect the aforementioned levels. Results: Neopterin, Kynurenine and KYN/TRP measurements in the patient group were found to be statistically significantly higher than the healthy control group; Bioterin and neopterin/bioterin ratios and TRP level; TNF-α (ng/L), KS (ng/mL), IFN-γ (ng/mL), IL6 (ng/L), C6S (ng/mL), IL1-B (pg/mL) levels did not show statistically significant differences between the groups. Conclusion: The data obtained from our study have helped elucidate the inflammatory process involved in the pathogenesis of Mucopolysaccharidosis Type 4 disease. This understanding paves the way.