A decade of molecular diagnosis of Mucolipidosis II and III in Brazil: a pooled analysis of 32 patients

Abstract GlcNAc-1-phosphotransferase is a hexameric complex formed by subunits α, β, and γ, where the first two are encoded by the GNPTAB gene and the third by the GNPTG gene. Pathogenic variants identified in the GNPTAB gene cause the diseases Mucolipidosis II and III alpha/beta, which are severe and characterized by an overflow of lysosomal hydrolases into the extracellular environment, and their absence in lysosomal compartments causes an accumulation of non-degraded macromolecules. Methodology: a retrospective study that included 32 unrelated Brazilian patients with a clinical and genetic diagnosis of Mucolipidosis II/III alpha/beta. The regional frequency of the altered alleles was determined. Results: The patients were from all regions of Brazil. The most prevalent variants were c.3503_3504del, associated with the severe form of the disease, and c.1208T>C, associated with the milder form. Variant c.3503_3504del is the most frequently found in the Midwest, Northeast, and Southeast regions of Brazil. In the South, 42.8% of the alleles present the c.1196C>T variant. Conclusions: From the perspective of all patients diagnosed with Mucolipidosis II/III in Brazil, it is possible to conclude that different regions present allelic frequencies of specific pathogenic variants, which can be explained by the occurrence of a founding effect or high inbreeding rates.

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis.

BACKGROUND: Serotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease. METHODS: We performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data. RESULTS: Two published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2-75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7-76.9%]). No heterogeneity was observed. CONCLUSIONS: Currently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.