2‐Deoxy‐ d ‐glucose uptake and fatty acid content in fibroblast cultures from children with syndromic paucity of interlobular bile ducts (alagille syndrome)

Summary 2‐Deoxy‐ d ‐glucose (2‐DOG) uptake was studied in skin fibroblast cultures from control children and children with Alagille syndrome or syndromic paucity of interlobular bile ducts (PILBD). No significant differences in uptake were observed between patients and controls. However, as the scatter of the results was larger in the fibroblasts from patients, we attempted to establish for these patients a relationship between 2‐DOG uptake and some biochemical parameters. We observed an inverse relationship between this uptake and the levels of plasma cholesterol and phospholipids ( r =−0.85). Compared to controls, 2‐DOG uptake was significantly lower in cultures from patients who had very high levels of cholesterol (P2 group), but not in cultures from patients with moderately increased levels of cholesterol (P1 group). The level of total cellular cholesterol in cultured cells from the P1 and P2 groups was not significantly different from the control level, but we found marked differences between the concentrations of fatty acids. In the cultures from patients (especially the P2 group), we observed a significant increase in total fatty acids; among the saturated fatty acids, this increase chiefly concerned the 18:0 (14%) and among the polyunsaturated the n −3 fatty acids (55%). The high concentrations of 20:5, 22:5 and 22:6, which enhance membrane fluidity, might explain the decrease in 2‐DOG uptake found in the cultures from patients (P2 group) with PILBD. The nature of these abnormalities might be connected with the genetic origin of Alagille syndrome