Tissue accumulation of sulfatide and GM3 ganglioside in a patient with variant Farber disease.
We analyzed the lipids in the tissues of a patient with an atypical form of Farber disease who developed several clinical symptoms not seen in patients with typical Farber disease (acid ceramidase deficiency). Lipids were extracted from formalin-fixed brain, liver and kidney and purified by ion exchange and silica gel column chromatographies and further by high-performance liquid chromatography on a silica gel column. We performed structural and quantitative analyses of three lipids named lipids X, Y and Z. Lipid X accumulated in the liver but not in the brain. Accumulation of lipids Y and Z was observed in liver and kidney. The content of lipid Y in the patients liver was more than ten times that in a control. The structures of lipids X, Y and Z were confirmed by means of 1H-nuclear magnetic resonance spectroscopy, fast atom bombardment mass spectrometry, infrared absorption spectroscopy, and component analysis involving gas liquid chromatography and gas chromatography-mass spectrometry. The structures of lipids X, Y and Z were identified as those of ceramide, sulfatide and GM3 ganglioside, respectively. These results suggest two possibilities. One is that the accumulation of glycolipids such as sulfatide and GM3 ganglioside is a secondary event produced by the accumulation of ceramide due to ceramidase deficiency. The other is that the accumulation of glycolipids other than ceramide is due to a deficiency of sphingolipid activator proteins which may affect the degradation of sulfatide and GM3 ganglioside as well as ceramide.
Fujiwaki
T
T
Department of Pediatrics, Tsuwano Kyozon Hospital, Japan.
Hamanaka
S
S
Tate
S
S
Inagaki
F
F
Suzuki
M
M
Suzuki
A
A
Mori
C
C
D055573:Acid Ceramidase; D000581:Amidohydrolases / Q000172:deficiency*; D002241:Carbohydrates / Q000032:analysis; D055572:Ceramidases; D002852:Chromatography, Ion Exchange; D002855:Chromatography, Thin Layer; D005679:G(M3) Ganglioside / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013106:Sphingolipidoses / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000378:metabolism*
D002241:Carbohydrates; D005679:G(M3) Ganglioside; D008055:Lipids; D013433:Sulfoglycosphingolipids; D000581:Amidohydrolases; C526693:ASAH1 protein, human; D055573:Acid Ceramidase; D055572:Ceramidases