Biomarkers in Glycogen Storage Diseases: An Update.

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.

Effect of VSL#3 Probiotic in a Patient with Glycogen Storage Disease Type Ia and Irritable Bowel Disease-like Disease.

Gut Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal disorders characterised by relapsing and remitting inflammation of the gastrointestinal tract. The two most common types of IBDs are ulcerative colitis and Crohn's disease. Patients with glycogen storage disease (GSD) type Ia present with gastrointestinal symptoms such as recurrent abdominal pain, bloating and changes in stool form or frequency, which is clinically difficult to distinguish from IBD. We report the case of a 36-year-old man with GSD type Ia and IBD-like disease. A commercial probiotic (VSL#3®) was chosen as a nutritional supplement treatment because of its high content of microbial species and strains. Three different tests were performed: normal-dose, no-dose and half-dose tests. The study periods for the normal-dose, no-dose and half-dose tests were 4 weeks from the treatment initiation, 72 h from the end of the previous period and 4 weeks to 6 months after the end of the 72-h period, respectively. When the probiotic treatment was stopped, he experienced several symptoms similar to those before the start of the treatment. The intestinal symptoms were less severe with the half-dose nutritional supplement treatment than with no treatment. Probiotics may reduce the number of irritable gut episodes and improve the patient's well-being and overall quality of life. More studies are needed to determine whether the improvement in more severe cases of GSD is due mainly to changes in the composition of the gut microbiota, as in this patient.

Recent advances in melanoma research via "omics" platforms.

Melanoma has a high mortality rate and metastatic melanoma is highly resistant to conventional therapies. "Omics" fields such as proteomics and microRNA and exosome studies have provided new knowledge to complement the information generated by genomic studies. This work aimed to review the current status of biomarker discovery for melanoma through multi-"omics" platforms. A few sets of novel microRNAs and proteins are described, some of them with important implications in suppressing melanoma at different stages. Upregulation of genes involved in angiogenesis, immunosuppressive factors, modification of stroma, capture of melanoma cells in lymph nodes and factors responsible for tumour cell recruitment have been identified in exosomes, among molecules with other functions. A remarkable series of proteins involved in epithelial-mesenchymal/mesenchymal-epithelial transitions, inflammation, motility, proliferation and progression processes, centrosome amplification, aneuploidy, inhibition of CD8+ effector T-cells, and metastasis in general were identified. Genomic and protein-protein interactions or metabolome levels were not analysed. Proteomics tools such as Orbitrap shotgun mass spectrometry or deep mining proteomic analysis utilizing high-resolution reversed phase nanoseparation in combination with mass spectrometry are also discussed. The application of these tools together with bioinformatics approaches applied to the clinical setting will enable the implementation of personalized medicine in the near future.