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Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
Congenital disorders of glycosylation (CDG) are a group of inherited conditions, usually presenting as multi-organ disease, and often affecting the CNS. The most frequently diagnosed deficiency of phosphomannomutase deficiency, PMM-CDG, presents with the diagnostic triad of cerebellar hypoplasia, abnormal fat pads and inverted nipples (Figs 14.30–14.32). Very few CDG disorders (over 50 genetic disorders are known) present with normal neurological development. In PMI-CDG, due to phosphoisomerase deficiency, patients primarily present with gastrointestinal symptoms (failure to thrive, protein-losing enteropathy and liver fibrosis). Other CDG diseases, belonging to the group of muscular dystroglycanopathies, affect primarily the muscle, brain and eye.
Carbohydrate and glycosylation disorders
Published in Steve Hannigan, Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
This condition is one of a group of disorders in which there are abnormal oligosac-charides (sugar chains). This is due to a deficiency or an absence of an enzyme known as phosphomannomutase. The oligosaccharides attach to proteins to form glycopro-teins. Glycoproteins have several important functions, including signalling how cells in the body interact with one another, aiding the transfer of nutrients around the body, playing a part in the coagulation of blood, and acting as hormones that regulate certain activities or organs in the body. Because the oligosaccharides are abnormal in this condition, the functions of the glycoproteins are afected, and this results in the symptoms of carbohydrate-deicient glycoprotein syndrome.
PMM2-CDG (Congenital disorders of glycosylation, type Ia)
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The defect in phosphomannomutase [4, 5] (see Figure 101.1) can be directly assayed in fibroblasts or leukocytes. In 16 patients, leukocyte activity ranged from 0.02 to 0.08 mU/mg protein as compared with the control range of 1.6 to 2.3. In fibroblasts, the range was 0.1 to 1.4 in patients and 2.2 to 6.4 in controls. In some cases, PMM2-CDG patients, even with severe clinical phenotype, presented with only intermediately reduced phosphomannomutase activities. In any case of suspected PMM2-CDG with an abnormal CDG-I transferrin pattern and only moderately reduced phosphomannomutase activity, genetic analysis of the PMM2 gene should be performed. The gene for phosphomannose-2 [26], designated PMM2, is localized on chromosome 16p13.3–p13.2, spanning 51.5 kb in eight exons and coding for 246 amino acids. At this point, more than 100 mutations have been described, mostly missense mutations. The disease is pan-ethnic, but different populations have their own set of mutations [31]. The most common mutations are R141H and F119L, accounting for approximately 37 and 17 percent of alleles, respectively; the R141H mutation is found in the compound heterozygous state in approximately 40 percent of patients of Caucasian origin [32], and the combination R141H/F119L accounts for about 38 percent of Caucasian patients. The R141H mutation has never been found in a homozygous state, presumably because that condition is incompatible with life. Patients with the R141H/F119L genotype represent the more severe end of the clinical spectrum. Pathogenic variants at the C-terminal, including p.His218Leu, p.Thr237Met, and p.Cys241Ser, may be associated with a milder phenotype [31, 33]. The F119L mutation has a clear founder effect in the Scandanavian population, and the R141H mutation is associated with a specific haplotype which points to a single ancient mutational event. The observed frequency of the R141H allele (one in 72) in normal populations of Netherlands and Denmark, and the observed frequency of that allele in the compound heterozygous state with other mutations, suggests the frequency of the disease in that population would be expected to be around 1 in 20,000. The incidence in that population, however, has been estimated to be more in the order of 1 in 80,000 [33, 34].
Stenotrophomonas maltophilia biofilm: its role in infectious diseases
Published in Expert Review of Anti-infective Therapy, 2019
Samantha Flores-Treviño, Paola Bocanegra-Ibarias, Adrián Camacho-Ortiz, Rayo Morfín-Otero, Humberto Antonio Salazar-Sesatty, Elvira Garza-González
Polysaccharides are components of the extracellular matrix of bacterial biofilms that also play a role in resistance to antibiotics [7]. Several gene products are implicated in the formation of the intermediates of LPSs and exopolysaccharides present in the bacterial cell outer membrane, which consequently may be involved in biofilm formation (Table 1). The spgM gene is a homologue of the algC gene, responsible for alginate biosynthesis in Pseudomonas aeruginosa. In S. maltophilia, this gene encodes a bifunctional enzyme with phosphoglucomutase and phosphomannomutase activities involved in LPS production, which contributes to antimicrobial resistance and virulence [15]. The spgM gene renders high biofilm production in both CF and non-CF S. maltophilia strains [16], with high prevalence in these strains (71.6–100%) [16–19].
Identification and characterization of a locus putatively involved in colanic acid biosynthesis in Vibrio alginolyticus ZJ-51
Published in Biofouling, 2018
Xiaochun Huang, Chang Chen, Chunhua Ren, Yingying Li, Yiqin Deng, Yiying Yang, Xiongqi Ding
Nucleotide sugars are the active form of sugars used as building blocks, so the production of nucleotide sugars is often the first step in polysaccharide synthesis. In EPSC, three pathways for nucleotide sugars were identified. The first contained the predicted genes, ORF19, ORF18, ORF16, ORF13, ORF15 and ORF14, coding mannose-6-phosphate isomerase (ManA), phosphomannomutase (ManB), mannose-1-phosphate guanyltransferase (ManC), GDP-mannose-4,6-dehydratase (Gmd), GDP-mannose mannosyl hydrolase (WcaH), and GDP-fucose synthetase (WcaG), respectively. They together catalyze the conversion of fructose-6-P to GDP-fucose. The second pathway participates in catalyzing Glc-1-P to UDP-glucose by ORF21-encoded GalU (UTP-glucose-1-phosphate uridylyltransferase). The third is to convert UDP-Glc to UDP-glucuronic acid by ORF20-encoded Ugd (UDP-glucose 6-dehydrogenase).