Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy

INTRODUCTION: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). METHODS: Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV(1)) and FEV(1)/FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. RESULTS: Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6–61) years in men, 34 (13–67) in women) were included. The greatest decrease of FEV(1)/FVC z-scores was observed in Classic men (−0.048 per year, 95% CI −0.081 to –0.014), compared with the Later-Onset men (+0.013,95% CI −0.055 to 0.082), Classic women (−0.008, 95% CI −0.035 to +0.020) and Later-Onset women (−0.013, 95% CI −0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV(1) decline. FEV(1)/FVC z-score decrease was significantly reduced after initiation of ERT initiation (−0.045 compared with −0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. CONCLUSION: Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.