Lysosomal accumulation of phospholipids in mucolipidosis IV cultured fibroblasts

Pulse-chase studies were performed to investigate the metabolism of phosphatidylethanolamine (PEA) in cultured fibroblasts from patients with mucolipidosis type IV (MLIV) and normal controls. When cultured cells were incubated with ³H-ethanolamine, 80-90% of the intracellular radioactivity was associated with PEA. Compared to the metabolism of ³H-PEA in normal cells, the phospholipid was retained in greater amounts and degraded more slowly in the MLIV fibroblasts. The ³H-PEA concentration in lysosomal preparations isolated by Percoll gradients was more than 3-fold greater in MLIV than in normal cells after 10 days chase. These studies indicate that PEA catabolism is deranged in MLIV and suggest that the primary metabolic defect causes abnormal phospholipid catabolism in the lysosomes of affected individuals.