Impaired energy metabolism in platelets from patients with Wiskott-Aldrich syndrome.

The platelet function defect seen in patients with Wiskott-Aldrich syndrome (WAS) has been ascribed to abnormal mitochondrial energy generation. The present study reveals a reduced energy content and low adenylate energy charge in platelets from two WAS-patients. Energy consumption in the resting platelets is slightly beyond the normal range, especially when ATP-resynthesis is primarily glycolytic. When platelets are stimulated with thrombin, the increase in energy consumption is 40-60% lower than in controls, both when energy is produced in glycolysis as when the mitochondria supply most of the energy. Analysis of the electron transport chain reveals no abnormalities. In contrast, the balance between glycolytic and mitochondrial ATP resynthesis is disturbed with a lowered contribution of oxidative ATP production. No such abnormalities are found in two WAS-carriers with the exception of a slight impairment in energy consumption during stimulation with thrombin. Thus, the platelet malfunction in WAS may be caused by a defect in the regulation of energy generation.