Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sialuria and sialidosis represent the two known types of genetic errors of sialic acid metabolism. Sialuria type I (or "massive Sialuria") remains a very rare disease, characterized by the daily excretion of 10 g of N-acetylneuraminic acid. Although the primary defect has not been established, the absence of a feedback inhibition of the anabolic reactions is probably involved in the massive production of free sialic acid. Sialuria type II (Salla disease) and type III are lysosomal storage diseases and the patients have shown to have a 10 to 15 fold increase in the amount of free sialic acid in urine. These sialurias probably involve a defect in translocation of sialic acid from lysosomes to the site of biosynthesis. The sialidase deficiency has been found to be responsible of a number of storage diseases previously unclassified or described as "lipomucopolysaccharidosis" or "mucolipidosis I". The sialidase deficiency, or Sialidosis, is characterized by and increased urinary excretion of sialyloligosaccharides and storage of sialylated compounds. A third type of genetic error, the combined beta-galactosidase-sialidase deficiency, is due to the genetic deficiency of a 32 KD "protective protein" which is part of the complex formed between multimeric beta-galactosidase and sialidase.
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PMID:[Genetic disorders of N-acetylneuraminic acid metabolism: sialurias and sialidoses]. 293 84

Sialidosis is an autosomal recessive disease resulting from a deficiency of lysosomal sialidase. Type II sialidosis is a rare disease characterized clinically by hydrops fetalis, hepatosplenomegaly, and severe psychomotor retardation. Genomic DNA from four unrelated sialidosis patients was screened for mutations within the sialidase gene NEU1. Five novel mutations were identified. Four are missense and one is nonsense: c.674G>C (p.R225P), c.893C>T (p.A298V), c.3G>A (p.M1?), c.941C>G (p.R341G), and c.69G>A (p.W23X). We have used our findings and diagnostic tools to confirm the presence of a homozygous null allele in a neonate sibling. Recombinant adenoviruses expressing the mutant sialidase alleles in primary cell cultures were utilized to assess the impact of each mutation on enzyme activity and intracellular localization. None of the mutant alleles expressed significant enzymatic activity. The p.R341G mutation exerts its pathological effect by perturbing substrate binding, while the p.A298V and p.R225P mutations appear to impair the folding of the sialidase enzyme. Our findings point to mutation-sensitive amino acids involved in catalytic function or structural stability and indicate the potential utility of these mutations for molecular diagnosis of this rare disease.
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PMID:Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression. 1469 30