The Wiskott-Aldrich syndrome: studies on a possible defect in mitochondrial ATP resynthesis in platelets

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Abstract
A possible defect in mitochondrial ATP resynthesis in platelets has been used for detection of Wiskott-Aldrich syndrome carriers (Shapiro). The detection was based on an abnormal adrenaline [epinephrine]-induced platelet aggregation under conditions that only the mitochondria provide metabolic energy. The test was evaluated and false negative and false positive results were found which raised doubts about the applicability of the test and the nature of the underlying defect. Direct analysis of mitochondrial ATP regeneration in patients and carriers showed an impaired mitochondrial energy production which was insufficient to maintain ATP homeostasis when glycolytic energy production was inhibited. Also abnormal was the fall in metabolic ATP concentration during stimulation with adrenaline and especially with thrombin when the platelets were incubated in glucose-free medium. These data provide direct evidence for a regulation defect in mitochondrial ATP resynthesis in platelets of patients and carriers with Wiskott-Aldrich syndrome.