Evaluation of the Inflammatory Process in Mucopolysaccharidosis Type IV A Patients Under Long-Term Enzyme Replacement Therapy

Mucopolysaccharidosis type IV A (MPS IVA) is an inborn error of the metabolism (IEM) caused by a deficiency of the enzyme N-acetylgalactosamine 6-sulfate sulfatase which can be treated with enzyme replacement therapy (ERT). There are reports of oxidative stress in the pathogenesis of MPS IVA. Since the inflammatory process is closely related to oxidative damage, this study investigated the mechanisms of inflammation in patients with MPS IVA during long-term ERT.

The plasma pro and anti-inflammatory cytokine concentrations (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α) were measured using the Cytokine Human Magnetic 10-Plex Panel Kit (Invitrogen) in the blood samples of 5 patients during treatment (median age 7.8 years, range 4−14 years) and 6 age-matched healthy children (median age 7.6 years, range 4.7−12 years). The median treatment duration was 4.8 years.

There was no significant difference between the MPS IV A and control groups regarding the production of proinflammatory cytokines. Regarding the anti-inflammatory cytokines, IL 10 was elevated in MPS IVA patients compared to the control group, demonstrating a difference in the regulation of the inflammatory process in these patients.

The ERT aims to reduce GAG accumulation, improving the patient`s quality of life. The patients’ GAG values were obtained from their medical records, with most patients having levels of urinary GAGs close to normal or within the normal range compared to reference values.

In conclusion, we reported for the first time that there is no significant increase in the inflammatory response in MPS IVA patients under long-term ERT, demonstrating the protective effect of the treatment and the importance of starting treatment in the early stages of the disease.