ABSENT PERIPHERAL CHEMOSENSITIVITY IN PRADER-WILLI-SYNDROME

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventil atory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 /- 1.4 kg/m(2)] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subject s had normal resting end-tidal PCO2 and arterial O-2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilato ry responses to 100% O-2 breathing, five tidal breaths of 100% N-2, an d vital capacity breaths of 15% CO2 in O-2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, P WS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical re sponse to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, P WS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N-2 breathing, again PWS p atients showed no change and control subjects exhibited a marked incre ase (P < 0.00005) in VE. We conclude that PWS patients have absent per ipheral chemoreceptor ventilatory responses. We speculate that the lac k of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.