Hepatic ganglioside abnormalities in a patient with familial erythrophagocytic lymphohistiocytosis.

Familial erythrophagocytic lymphohistiocytosis (FEL) is an autosomal recessive disease of unknown pathogenesis. Because of evidence of increased circulating and hepatic lipids in FEL, we performed a comprehensive analysis of the hepatic lipids of a patient with this disease. In contrast to normal qualitative characteristics and to normal or only mildly elevated concentrations of total lipids, neutral lipids, phospholipids, and neutral glycosphingolipids, this study reports a significant elevation of acidic glycosphingolipids, gangliosides (387 versus 147 nmole lipid-bound sialic acid/g wet weight, patient versus control). This quantitative abnormality was unusual in that it included disproportionately increased concentrations of most of the minor hepatic ganglioside species rather than either a marked increase in one single or a generalized nonspecific increase in all gangliosides, which is characteristic of known disorders exhibiting hepatic ganglioside storage. Activities of the hepatic lysosomal glycosylhydrolases which are important in ganglioside metabolism were therefore assessed by using artificial substrates. Of the enzymes tested, beta-galactosidase activity alone was remarkable, being moderately reduced (33% of that of the normal liver); no biochemical explanation for the reduction was found. The findings suggest FEL may be associated with a unique quantitative and qualitative abnormality in hepatic gangliosides, the cause of which remains to be elucidated.