hymecromone and Glycogen-Storage-Disease

We report on a 2-yr-old boy with progressive muscular weakness and respiratory failure. There was no clinical evidence of heart muscle involvement. Autopsy showed marked intralysosomal glycogen deposition in skeletal muscle and liver with no histological evidence of glycogen deposition in cardiac muscle. The activity of the lysosomal enzyme alpha-1,4-glucosidase was deficient in skin fibroblasts, skeletal muscle, cardiac muscle, and liver; however, the enzymatic activity in peripheral blood leukocytes was in the low normal range. The child's mother had normal enzymatic activity in leukocytes but heterozygote levels in skin fibroblasts.

Topics: alpha-Glucosidases; Child, Preschool; Fibroblasts; Genes, Recessive; Genetic Variation; Glucosides; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Hymecromone; Leukocytes; Male; Muscles; Muscular Diseases; Respiratory Insufficiency

The diagnosis of Pompe's disease by the assay of acid alpha-glucosidase in kidney and leucocytes was not previously possible because of the presence of another component which had activity at pH 4.0, but was not deficient in the disease. This problem was resolved either by the use of the inhibitors, turanose, maltose and citrate, or by isoelectric precipitation at pH 5.0, which enabled the estimation of acid alpha glucosidase in kidney and leucocytes.

Topics: alpha-Glucosidases; Glucosides; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Hymecromone; Kidney; Leukocytes; Umbelliferones

The possible interference of neutral alpha-D-glucosidase in the diagnosis of Pompe's disease using 4-methylumbelliferyl-alpha-D-glucopyranoside as substrate for the assay of acid alpha-D-glucosidase was investigated. The pH profile of alpha-D-glucosidase in control skin fibroblasts and amniotic fluid cells showed two peaks of activity. The shape of the pH profile depended upon whether or not the extract was added to the buffer before the substrate. If extract was added to the buffer before the substrate, a greater separation was obtained between the two peaks of activity. The neutral alpha-D-glucosidase activity could be totally removed by preliminary precipitation at pH 5.0. Following acid region whilst Pompe's cells had no activity enabling a clear distinction to be made between carriers and the disease state.

Topics: Amniotic Fluid; Cells, Cultured; Drug Stability; Female; Fibroblasts; Glucosidases; Glucosides; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Hydrogen-Ion Concentration; Hymecromone; Kinetics; Pregnancy; Prenatal Diagnosis; Skin