title: Clinical and biochemical analysis of two families with type I and type II mannosidosis.
abstract: We report on two unrelated patients with different presentations of mannosidosis. One patient was affected in early childhood with a severe phenotype characteristic of type I mannosidosis. The other was diagnosed with type II mannosidosis only after the onset of progressive neurologic deterioration in late adulthood. Both were detected by non-invasive urinary screening of oligosaccharides. Lymphoblasts transformed from both patients' blood cells had markedly reduced lysosomal alpha-mannosidase activity. Kinetic analyses showed that alpha-mannosidase from the type I patient had a 400-fold reduction in affinity while that from the type II patient was reduced 40-fold. Lymphoblasts from all 4 parents had reduced alpha-mannosidase activity, but there were overlapping activities among these type I and type II obligate heterozygotes. We conclude that screening urinary oligosaccharides will detect mannosidosis over a wide range of phenotypes, that lymphoblasts transformed from affected heterozygotes have decreased enzymatic activity, and that the severity of clinical expression is related to the degree of enzyme impairment.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Bennet
authors.forename: P P
authors.initials: PP
authors.lastname: Dembure
authors.forename: L J
authors.initials: LJ
authors.lastname: Elsas
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004796:Clinical Enzyme Tests; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D007700:Kinetics; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008361:Mannosidases / Q000172:deficiency*; D009844:Oligosaccharides / Q000652:urine; D013379:Substrate Specificity; D043323:alpha-Mannosidase; D008363:alpha-Mannosidosis / Q000175:diagnosis* / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000097:blood
chemical_list: D009844:Oligosaccharides; D008361:Mannosidases; D043323:alpha-Mannosidase; D001619:beta-N-Acetylhexosaminidases