Disease burden, management patterns and multidisciplinary clinical approaches for patients with MPS IVA and VI in selected Latin American Countries.

BACKGROUND: There is a paucity of real-world epidemiological data on patients with mucopolysaccharidoses (MPS) in Latin America. This real-world study assessed the disease burden, management patterns and multidisciplinary clinical approaches for MPS-IVA and MPS-VI patients in Latin America (Colombia, Ecuador, Mexico, Peru). METHODS: Data were collected from physicians/specialists experienced in treating MPS patients between April-June 2020, via an online patient-diary survey. RESULTS: Overall, 29 physicians/specialists participated in this study. Data from 98 patients were analyzed (MPS-IVA, 71 patients and MPS-VI, 27 patients). Mean age for MPS-IVA patients was 17.5 years and for MPS-VI patients was 11.6 years, and the majority were females (52% and 78%, respectively). MPS-IVA and VI patients presented a high absenteeism from school (55% and 37%, respectively; <18 years age) and workplace (78% and 100%, respectively; >18 years age), indicating an impact of the disease on some aspects of the patients' quality of life. The onset of the first symptom occurred at the age of 3.1 years for MPS-IVA patients and at 1 year for MPS-VI, with delay in diagnosis (3.5-3.9 years from symptom onset) and enzyme replacement therapy (ERT) initiation (1.1-3.6 years from diagnosis). ERT interruptions were observed for MPS-IVA (48%) and MPS-VI patients (44%), with non-availability of medication recorded as the main reason for non-adherence (46% and 60% patients, respectively). ERT showed noticeable treatment benefits in MPS-IVA/VI patients, with stabilization/reduction in complications or the number of surgeries. A multidisciplinary clinical team approach was used for patient management. CONCLUSION: The disease burden for MPS-IVA/VI was high in Latin America, with consistent management, treatment and socio-demographic trends throughout the region.

Biochemical similarity between cultured chondrocytes and in situ chondrocytes by chemometric analysis from FTIR microspectroscopy.

BACKGROUND AIMS: Fourier Transform Infrared Micro-spectroscopy (FTIRM) is an emerging tool that obtains images with biochemical information of samples that are too small to be chemically analyzed by conventional Fourier transform infrared (FTIR) spectroscopy techniques. So, the central objective of this project was to study the biochemical similarity between articular and cultured chondrocytes by chemometric analysis from FTIRM. METHODS: Nine samples of knee articular cartilage were obtained; each sample was divided into two fragments, one portion was used for FTIRM characterization in situ, and from another part, chondrocytes were obtained to be cultured (in vitro), which were subjected to an FTIRM to characterize their biomolecular components. The FTIRM spectra were normalized, and the second derivative was calculated. From these data, principal component analysis (PCA) and a chemometric comparison between in situ and cultured chondrocytes were carried out. Finally, the biochemical mapping was conducted obtaining micro-FTIR imaging. RESULTS: FTIRM spectra of in situ and in vitro chondrocytes were obtained, and different biomolecules were detected, highlighting lipids, proteins, glycosaminoglycans, collagen, and aggrecan. Despite slight differences in the FTIR spectra, the PCA proved the organic similarity between in situ chondrocytes and cultured chondrocytes, which was also observed in the analysis of the ratios related to the degradation of the articular cartilage and collagen. In the same way, the ability of the FTIRM to characterize the molecular biodistribution was demonstrated. CONCLUSION: The biochemical composition and biodistribution analysis using FTIRM have been useful for comparing cultured chondrocytes and in situ chondrocytes.

Oxidative profile exhibited by Mucopolysaccharidosis type IVA patients at diagnosis: Increased keratan urinary levels.

Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.