Fabry disease: reduced activities of respiratory chain enzymes with decreased levels of energy-rich phosphates in fibroblasts.
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.


RESULTS
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).


CONCLUSIONS
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.
Lücke
Thomas
T
Department of Pediatrics, Hannover Medical School, Carl-Neuberg Str. 1, D-30625 Hannover, Germany.
Höppner
Wiebke
W
Schmidt
Esther
E
Illsinger
Sabine
S
Das
Anibh M
AM
D000227:Adenine Nucleotides / Q000032:analysis / Q000172:deficiency*; D018929:Cell Culture Techniques; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000032:analysis / Q000378:metabolism*; D000795:Fabry Disease / Q000201:enzymology* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010725:Phosphocreatine / Q000172:deficiency
D000227:Adenine Nucleotides; D045222:Electron Transport Chain Complex Proteins; D010725:Phosphocreatine