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Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy
  1. Daniel Franzen1,
  2. Sarah R Haile2,
  3. David C Kasper3,
  4. Thomas P Mechtler3,
  5. Andreas J Flammer4,
  6. Pierre A Krayenbühl5 and
  7. Albina Nowak4
  1. 1 Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland
  2. 2 Epidemiology Department, University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Zurich, Switzerland
  3. 3 ARCHIMED Life Science, Vienna, Austria
  4. 4 University Heart Center, University Hospital Zurich, Zurich, Switzerland
  5. 5 Department of Internal Medicine, Linth Hospital, Uznach, Switzerland
  1. Correspondence to Dr Daniel Franzen; daniel.franzen{at}


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 (FEV1) and FEV1/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 FEV1/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 FEV1 decline. FEV1/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.

  • rare lung diseases
  • copd ÀÜ mechanisms
  • systemic disease and lungs

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  • Contributors Conception: DF, PAK, AN. Data collection: DF, AN. Data analysis and interpretation: DF, SRH, DCK, TPM, AJF, AN. Drafting of the article: DF, SRH, AN. Critical revision: PAK, DCK, TPM, AJF. Final approval: all authors.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests AN is a consultant to Shire, received lecturing honoraria and research support from Sanofi Genzyme and Shire, and received financial publication support of this paper from Sanofi Genzyme.

  • Patient consent Obtained.

  • Ethics approval KEK-ZH 2012-0115.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data can be requested from the first or last author by email.

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