title: Unusual clinical and ultrastructural features in a boy with biochemically typical mannosidosis.
abstract: A 4 1/2-year-old boy with a history of recurring respiratory tract infections and seizures, and evidence of severe retardation of psychomotor development and growth, lacked the coarse facial features, skeletal changes and other clinical stigmata generally associated with mannosidosis, but the total alpha-mannosidase activity in his leukocytes, cultured fibroblasts and liver were no more than 10% of the control mean. Studies of the residual alpha-mannosidase enzyme suggest a specific deficiency of the thermostable isoenzyme with an acidic pH optimum. The alpha-mannosidase in the fibroblasts of our and another (control) patient with mannosidosis had a reduced affinity for the substrate 4-methylumbelliferyl-alpha-D-mannoside. Light microscopy of the liver biopsy showed an increase in connective tissue often distorting the hepatic architecture; numerous tiny vacuoles, small dense and lipid bodies in most hepatocytes, and similar but more extensive changes in sinusoidal cells; and sinusoidal pools of hepatocytic debris. Electron microscopy of hepatocytes revealed vacuoles similar but not identical to those described in reported mannosidosis patients, and in addition several forms of secondary lysosomes; prominent peroxisomes (microbodies); increased numbers of profiles of smooth endoplasmic reticulum; dilated rough endoplasmic reticulum containing traces of fine granulo-fibrillar material; increased numbers of rosettes of alpha particles of glycogen and reduced numbers of mitochondria with alterations in their distribution, size and configuration. It is believed that the usual clinical and hepatic ultrastructural features in our patient reflect another variant of mannosidosis.
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology; D002675:Child, Preschool; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008361:Mannosidases / Q000172:deficiency*; D009940:Organoids / Q000648:ultrastructure
chemical_list: D008361:Mannosidases