Mucopolysaccharidoses are extremely rare, progressive, often severe multisystem disorders, some of which are managed by weekly intravenous enzyme replacement therapy. This study aimed to determine the difficulties faced by the patients with mucopolysaccharidosis and their families due to enzyme replacement therapy.A questionnaire about demographics, enzyme replacement therapy-related characteristics, and specific enzyme replacement therapy-related difficulties was conducted over the telephone with mucopolysaccharidosis patients (or their parents) followed at a referral center in Turkey, who have been on enzyme replacement therapy for ≥12 months. The responses were analyzed with chi-square, Mann-Whitney U, Kruskal-Wallis tests, Spearman's rank correlation, and binary logistic regression.A total of 54 patients (median age: 13 years) participated, who had been receiving enzyme replacemnt therapy for a median of 5.02 years, 83.3% of whom had mucopolysaccharidosis- IVA or -VI. About 72.2% went to school or work, 64.1% of whom missed a full day every week due to enzyme replacement therapy. About 63% missed at least 1 dose in the past 6 months, mostly due to not being able to obtain doses or having intercurrent infections. Significantly more enzyme replacement therapy doses were missed or unobtained in Central (non-Ankara) and Eastern Anatolia, but enzyme replacement therapy-related disruption to family life was more severe in families living in Ankara.We provide the first Turkish data about mucopolysaccharidosis patients' subjective enzyme replacement therapy experience, which is influenced by actionable inequalities and hurdles, partially related to geographical factors. Access to the drugs can be facilitated, and the clash of enzyme replacement therapy infusions with school and work should be avoided. Multi-center studies using more objective data sources are needed.