Trying to disentangle the causes of dyspnea and exercise limitation in a subject with GATA2 deficiency and normal spirometry: a case report

Background GATA-binding factor 2 (GATA2) deficiency is a genetic disorder characterized by prominent infectious and noninfectious pulmonary manifestations. Even though most patients with GATA2 deficiency seek medical attention for dyspnea and exercise intolerance, lung function data for this syndrome are scarce and rather inconclusive. Objective To provide a comprehensive examination of lung function and quantitative computed tomography (CT) data and to assess responses to incremental exercise in a 38.5-year-old man with GATA2 deficiency and myelodysplastic syndrome, breathlessness, and normal spirometry. Methods Lung volumes, spirometry, and single breath lung diffusing capacities for carbon monoxide (DL CO ) and nitric oxide (DL NO ) were sequentially measured. Subsequently, mean expired and arterial partial pressures of O 2 and CO 2 were obtained. The subject then performed a continuous (ramp-pattern) incremental [25 watts (W)·min –1 ] exercise test to a symptom-limited maximum on an electronically braked cycle ergometer. Results Dyspnea and exercise intolerance were associated with 1) anemia, 2) severe impairment of alveolar-to-capillary gas diffusion with CT changes characterized by diffuse paraseptal emphysema and interstitial lung abnormalities associated with active Pneumocystis jirovecii infection, and 3) abnormal responses to incremental exercise mainly due to a combination of mechanisms including decreased pulmonary gas exchange, anemia resulting in reduced blood O 2 -carrying capacity, metabolic acidosis, increased ventilatory drive, and deconditioning. Conclusions This case study illustrates how clinical medicine benefits from applying the basic principles of respiratory physiology both at rest and during exercise to discern the mechanisms of dyspnea and exercise intolerance.