TISSUE ACCUMULATION OF SULFATIDE AND G(M3) GANGLIOSIDE IN A PATIENT WITH VARIANT FARBER-DISEASE

We analyzed the lipids in the tissues of a patient with an atypical fo rm 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 fu rther by high-performance liquid chromatography on a silica gel column . We performed structural and quantitative analyses of three lipids na med 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 kidne y. The content of lipid Y in the patients liver was more than ten time s that in a control. The structures of lipids X, Y and Z were confirme d by means of H-1-nuclear magnetic resonance spectroscopy, fast atom b ombardment mass spectrometry, infrared absorption spectroscopy, and co mponent analysis involving gas liquid chromatography and gas chromatog raphy-mass spectrometry. The structures of lipids X, Y and Z were iden tified as those of ceramide, sulfatide and G(M3) ganglioside, respecti vely. These results suggest two possibilities. One is that the accumul ation of glycolipids such as sulfatide and G(M3) ganglioside is a seco ndary event produced by the accumulation of ceramide due to ceramidase deficiency. The other is that the accumulation of glycolipids other t han ceramide is due to a deficiency of sphingolipid activator proteins which may affect the degradation of sulfatide and G(M3) ganglioside a s well as ceramide.