phosphocreatine and Fabry-Disease

Fabry disease (FD, MIM 301500) caused by a deficient activity of alpha-galactosidase A is characterized by intralysosomal storage of glycosphingolipids. Main clinical features are paresthesia, hypohidrosis, angiokeratoma, renal insufficiency, and cardiovascular or cerebral complications. The exact pathogenesis is unclear. Beside mechanical storage biochemical factors might play a role. As FD is a multisystemic disorder and mitochondrial dysfunction has been described in patients with neuronal ceroidlipofuscinosis (another lysosomal storage disease) we examined mitochondrial function in fibroblasts from patients with FD.. Activities of respiratory chain enzymes I, IV, and V were significantly (p < 0.01) lower in FD-cells. Mitochondrial recovery was unchanged as judged by the activity of the mitochondrial marker enzyme citratesynthase, cellular protein content was not significantly different. CP, ADP, and AMP concentrations were significantly (p < 0.01) lower in FD-cells. ATP was slightly, but not significantly reduced (p = 0.045).. Organ dysfunction in FD may not only be explained by mechanical storage of glycosphingolipids. As in NCL, lysosomal storage material may lead to mitochondrial dysfunction with a reduction of respiratory chain enzyme activities and a subsequent drop in cellular levels of energy-rich phosphates.

Topics: Adenine Nucleotides; Cell Culture Techniques; Electron Transport; Electron Transport Chain Complex Proteins; Fabry Disease; Fibroblasts; Humans; Phosphocreatine