B61-05 Hypoventilation During Exercise in People With Congenital Central Hypoventilation Syndrome

Abstract Rationale There is a paucity of data on exercise in individuals with genetically confirmed congenital central hypoventilation syndrome (CCHS). We hypothesize that 1) these individuals hypoventilate at peak exercise and 2) PHOX2B gene variant and/or BMI do not contribute to their risk of hypoventilation during exercise. Methods We performed a retrospective study of individuals with genetically confirmed CCHS, aged 6 years, who were seen at Children’s Hospital Los Angeles (CHLA) between 2000 and 2025 and performed a cardiopulmonary exercise stress test (CPET). Data collected included demographics, BMI and BMI %ile, PHOX2B gene variant, type of ventilatory support, past medical history, polysomnography (PSG) and CPET results. Results Nine people with CCHS aged 8-22 years were included; six with a PHOX2B polyalanine repeat mutation (PARM) and three with a non-PARM. Three were obese and one was overweight. Seven of the subjects were ventilated during sleep via non-invasive positive pressure and two were ventilated via tracheostomy. All had an end tidal CO2 less than 40 torr from their most recent PSG. Two of the subjects had asthma, which was well-controlled. None had significant lung disease or ventilatory muscle weakness. Maximal oxygen consumption (Max VO2) was 24.9±10.9 mL/min/kg, indicating decreased aerobic capacity. Mean minute ventilation (VE) and VE/VO2 were low at maximal exercise. End tidal CO2 (PETCO2) increased from rest (33±6 torr) to maximal exercise (48±9 torr), reflecting hypoventilation at maximal exercise (p 0.0006). The difference in mean PETCO2 at peak exercise minus at rest was greater for PARM (19±6 torr) than for non-PARM (7±3 torr; p = 0.019). The mean PETCO2 at maximal exercise in patients who were overweight and obese was 51±9 torr, which is similar to that of those in the healthy weight range, 46±9 torr. Conclusion Individuals with CCHS, who were well ventilated during sleep, exhibit hypoventilation during exercise. Hypoventilation was worse in CCHS patients with a PARM compared to non-PARM. Hypoventilation was not affected by BMI. This abstract is funded by: None