title: Chromatofocusing of skin fibroblast sphingomyelinase: alterations in Niemann-Pick disease type C shared by GM1-gangliosidosis.
abstract: Sphingomyelinase activity of cultivated skin fibroblast extracts from normal individuals was resolved by chromatofocusing in the pH range 8-5 into three major components with pI's of 7.3, 6.3 and 5.9, respectively. Chromatofocusing proved a more efficient and reproducible separation technique than preparative flat-bed isoelectric focusing and it gave a constant profile even when detergent concentration varied. In skin fibroblasts from five patients with Niemann-Pick disease type C, a varying degree of reduction in the proportion of the 7.3 peak was observed. In a patient with clinical features of Niemann-Pick disease type C, the finding of such a profile would thus be a good argument for the diagnosis, but it is not pathognomonic as we found similar changes in two cases with GM1-gangliosidosis, while some cases of Niemann-Pick disease type C have borderline normal profiles. These results challenge the concept of a specific sphingomyelinase isoenzyme deficiency as the basic defect in Niemann-Pick disease type C.
mesh_terms: D005347:Fibroblasts / Q000201:enzymology*; D005677:G(M1) Ganglioside; D005733:Gangliosidoses / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D007526:Isoelectric Point; D009542:Niemann-Pick Diseases / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000302:isolation & purification*; D012867:Skin / Q000201:enzymology; D013108:Sphingomyelin Phosphodiesterase / Q000302:isolation & purification*
chemical_list: D005677:G(M1) Ganglioside; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase