Prominent increase in plasma ganglioside GM3 is associated with clinical manifestations of type I Gaucher disease

Patients with Gaucher disease show signs of insulin resistance. The ganglioside GM3 has recently shown to be a negative regulator of insulin sensitivity. In fibroblasts of Gaucher patients, deficient in degradation of glucosylceramide, an increased anabolism of this lipid to gangliosides occurs. The goal of the current study was to establish whether GM3 is elevated in plasma of type I Gaucher disease patients, and is related to disease manifestations. Plasma GM3, glucosylceramide, and ceramide were determined and compared to overall severity of disease, hepatomegaly, and plasma chitotriosidase activity. The ceramide concentration in plasma of untreated Gaucher patients was slightly but not significantly lower than in controls (median: 9.8 µmol/L, range: 5.7–14.7 µmol/L, (n=40) vs. median: 11.0 µmol/L, range: 5.1–18.0 µmol/L, (n=30)). Glucosylceramide was significantly (p