Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through re-analysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, and 9 had copy number variations, and 90 had novel variants. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962C>T, c.281C>A), GALNS (c.319G>A, c.860C>T, c.1042A>G), and IDUA (c.1A>C, c.1598C>G). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into the genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.

BackgroundThere is limited information about sociodemographic disparities in COVID‐19 vaccine uptake among non‐elderly adults with an increased risk of severe COVID‐19. We investigated the COVID‐19 vaccine uptake in individuals aged 18–64 years with an increased risk of severe COVID‐19 (non‐elderly risk group) in Stockholm County, Sweden.MethodWe used population‐based health and sociodemographic registries with high coverage to perform a cohort study of COVID‐19 vaccine uptake of one to four doses up until 21 November 2022. The vaccine uptake in the non‐elderly risk group was compared with non‐risk groups aged 18–64 years (non‐elderly non‐risk group) and individuals aged ≥65 years (elderly).ResultsThe uptake of ≥3 vaccine doses was 55%, 64% and 87% in the non‐elderly non‐risk group (n = 1,005,182), non‐elderly risk group (n = 308,904) and elderly (n = 422,604), respectively. Among non‐elderly risk group conditions, Down syndrome showed the strongest positive association with receiving three doses (adjusted risk ratio [aRR] 1.62, 95% confidence interval [CI] 1.54–1.71), whereas chronic liver disease showed the strongest negative association (aRR 0.90, 95% CI 0.88–0.92). Higher vaccine uptake among the non‐elderly risk group was associated with increasing age, being born in Sweden, higher education, higher income and living in a household where other adults had been vaccinated. Similar trends were observed for the first, second, third and fourth doses.ConclusionThese results call for measures to tackle sociodemographic disparities in vaccination programmes during and beyond the COVID‐19 pandemic.