N-acetylglucosamine 6-sulphatase deficiency in a Nubian goat: a model of Sanfilippo syndrome type D (mucopolysaccharidosis IIID).
A male Nubian goat (SD-1) presented at birth with neurological manifestations consistent with a lysosomal storage disease. Histological studies of tissue obtained at autopsy suggested glycosaminoglycan storage. Total urinary glycosaminoglycan levels, as measured by the uronic acid method, were elevated but overlapped with levels in a younger control goat. However, N-sulphate content was increased 2- to 5-fold, suggestive of heparan sulphate excretion, and this elevation was confirmed by cellulose acetate electrophoresis. Further, urinary levels of free N-acetylglucosamine 6-sulphate were increased 6-fold over controls, SD-1 cultured skin fibroblasts, labelled with [35S]sulphate from the incorporated twice as much radioactivity into macromolecular material as did normal fibroblasts. Forty-eight hours after removal of [35S]sulphate from the medium the SD-1 fibroblasts retained 58% of the label, whereas in control fibroblasts it had declined to 20%, indicative of [35S]proteoglycan storage in SD-1. The assay of fibroblast extracts revealed a profound deficiency of N-acetylglucosamine 6-sulphatase whereas eight other activities including beta-mannosidase, arylsulphatase B, iduronate 2-sulphatase, N-acetylgalactosamine 6-sulphatase, and heparin sulphamidase were normal. Mixing of SD-1 sonicates with normal sonicates showed no evidence of an inhibitor, and mixing of SD-1 sonicates with Sanfilippo D cell sonicates yielded no activity. These data ruled out multiple sulphatase deficiency and suggested the first example of the human Sanfilippo syndrome, type D (N-acetylglucosamine 6-sulphatase deficiency) in goats.
Thompson
J N
JN
Laboratory of Medical Genetics, University of Alabama, Birmingham 35294.
Jones
M Z
MZ
Dawson
G
G
Huffman
P S
PS
D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000652:urine; D000818:Animals; D004195:Disease Models, Animal; D004588:Electrophoresis, Cellulose Acetate; D005347:Fibroblasts / Q000201:enzymology; D006025:Glycosaminoglycans / Q000652:urine; D006041:Goats; D008297:Male; D009084:Mucopolysaccharidosis III / Q000175:diagnosis*; D013429:Sulfatases / Q000172:deficiency*; D013431:Sulfates / Q000378:metabolism
D006025:Glycosaminoglycans; D013431:Sulfates; C033137:N-acetylglucosamine-6-sulfate; D013429:Sulfatases; C018719:N-acetylglucosamine-6-sulfatase; D000117:Acetylglucosamine