Search Results (4)

Klebsiella oxytoca bacilli co-form the human intestinal microbiota, but in favorable conditions, they may also affect immunocompromised individuals, causing urinary tract infections, bacteremia, or antibiotic-associated hemorrhagic colitis. The growing numbers of clinical outbreaks of K. oxytoca infections make these bacteria an emerging pathogen, which is still masked by the predominant K. pneumoniae isolates. Thus, it is very important to advance knowledge on K. oxytoca pathogenicity. This work aims to characterize a urine isolate, K. oxytoca 0.062, from central Poland, which appears to present a multidrug-resistant and extended-spectrum β-lactamases-positive phenotype. The structural experiments include sugar and methylation analyses, mass spectrometry, and ¹H and ¹³C Nuclear Magnetic Resonance (NMR) spectroscopy. Additionally, ¹H,¹H ROESY, and ¹H,¹³C HMBC experiments were carried out on the high-molecular-weight O polysaccharide fraction of K. oxytoca lipopolysaccharides (LPSs). These analyses led to the detection of two polysaccharide antigens: one neutral, containing a linear trisaccharide unit called mannan, and one acidic, which is built up of a branched tetrasaccharide unit containing two mannopyranose (α-Manp) residues, one galactopyranose (β-Galp) residue, and one galacturonic acid (α-GalpA) residue. The GalpA residue seems to be a potential minor epitope, recognized by the selected Proteus antisera in the serological studies. Full article

In recent years, there has been a significant increase in the diagnosis of asymptomatic Late-Onset Pompe Disease (LOPD) patients, who are detected via family screening or Newborn Screening (NBS). The dilemma is when to start Enzyme Replacement Therapy (ERT) in patients without any clinical sign of the disease, considering its important benefits in terms of loss of muscle but also its very high cost, risk of side effects, and long-term immunogenicity. Muscle Magnetic Resonance Imaging (MRI) is accessible, radiation-free, and reproducible; therefore, it is an important instrument for the diagnosis and follow-up of patients with LOPD, especially in asymptomatic cases. European guidelines suggest monitoring in asymptomatic LOPD cases with minimal MRI findings, although other guidelines consider starting ERT in apparently asymptomatic cases with initial muscle involvement (e.g., paraspinal muscles). We describe three siblings affected by LOPD who present compound heterozygosis and wide phenotypic variability. The three cases differ in age at presentation, symptoms, urinary tetrasaccharide levels, and MRI findings, confirming the significant phenotypic variability of LOPD and the difficulty in deciding when to start therapy. Full article

Following clinical indications, the laboratory diagnosis of the inherited metabolic myopathy, Pompe disease (PD), typically begins with demonstrating a reduction in acid alpha-glucosidase (GAA), the enzyme required for lysosomal glycogen degradation. Although simple in concept, a major challenge is defining reference intervals, as even carriers can have reduced GAA, and pseudodeficiencies complicate interpretation. Here, we developed a mass spectrometric assay for quantification of a urinary glycogen metabolite (tetrasaccharide) and reported on its utility as a confirmatory test for PD in a diagnostic laboratory. Using two age-related reference intervals, eight returned tetrasaccharide concentrations above the calculated reference interval but did not have PD, highlighting non-specificity. However, retrospective analysis revealed elevated tetrasaccharide in seven infantile-onset (IOPD) cases and sixteen late-onset (LOPD) cases, and normal concentrations in one heterozygote. Prospective tetrasaccharide analysis in nine individuals with reduced GAA confirmed IOPD in one, LOPD in six and identified two heterozygotes. Using this metabolite as a biomarker of therapeutic response was not overly informative; although most patients showed an initial drop following therapy initiation, tetrasaccharide concentrations fluctuated considerably and remained above reference intervals in all patients. While useful as a confirmation of PD, its utility as a biomarker for monitoring treatment warrants further investigation. Full article

Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. In this study we reviewed the literature from 1977 to 2020 concerning GSDs, biomarkers, and metabolic imbalances in the symptoms of some GSDs. Most of the reported studies were performed with very few patients. Classification of emerging biomarkers between different types of diseases (hepatics GSDs, McArdle and PDs and other possible biomarkers) was done for better understanding. Calprotectin for hepatics GSDs and urinary glucose tetrasaccharide for Pompe disease have been approved for clinical use, and most of the markers mentioned in this review only need clinical validation, as a final step for their routine use. Most of the possible biomarkers are implied in hepatocellular adenomas, cardiomyopathies, in malfunction of skeletal muscle, in growth retardation, neutropenia, osteopenia and bowel inflammation. However, a few markers have lost interest due to a great variability of results, which is the case of biotinidase, actin alpha 2, smooth muscle, aorta and fibroblast growth factor receptor 4. This is the first review published on emerging biomarkers with a potential application to GSDs. Full article