title: Immunoelectron microscopic analysis of lysosomal deposits in alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum.
abstract: Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency with angiokeratoma corporis diffusum (AKCD) is one of the lysosomal storage diseases. GalNAc(alpha))1-O-Ser/Thr (Tn) is theoretically deposited in lysosomes, but substances with attached galactose and neuraminic (sialic) acid (T and sialosyl Tn, respectively) are excreted in patients' urine. In this study, in two Japanese cases we analyzed the material accumulated in lysosomes using immunoelectron microscopy with mouse antibodies to Tn, sialosyl Tn and T (Thomsen-Friedenreich) antigens in order to find out what substance(s) is really deposited in lysosomes. We found that only GalNAc(alpha)1-O-Ser/Thr (Tn) was actually accumulated in vacuolated lysosomes of vascular endothelial cells, eccrine sweat gland cells, fibroblasts and pericytes. Galactosylation and sialylation of Tn appears to occur in cells other than those in the skin. The results suggest that this disease is caused by a single enzyme deficiency.
authors: Department of Dermatology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. dngr@f2.dion.ne.jp
authors: Akira
authors: A
authors: Kanda
authors: Shinichiro
authors: S
authors: Tsuyama
authors: Fusayoshi
authors: F
authors: Murata
authors: Kazuo
authors: K
authors: Kodama
authors: Yoshio
authors: Y
authors: Hirabayashi
authors: Tamotsu
authors: T
authors: Kanzaki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D000795:Fabry Disease / Q000201:enzymology*; D005260:Female; D006596:Hexosaminidases / Q000172:deficiency*; D006801:Humans; D007564:Japan; D008247:Lysosomes / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D048809:alpha-N-Acetylgalactosaminidase
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; C040286:Tn antigen; C055491:sialosyl-Tn antigen; C016467:Thomsen-Friedenreich antigen; D006596:Hexosaminidases; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase