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Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

ABSTRACT: Fabry disease (FD) is a lysosomal storage disorder leading to decreased ?-galactosidase A enzyme activity and subsequent abnormal accumulation of glycosphingolipids in various organs. Although histological evidence of lung involvement has been demonstrated, the functional impact of these changes is less clear.Adult patients with FD who had yearly pulmonary function tests (PFT) at two centers from 1999 thru 2015 were eligible for this observational study. Primary outcome measures were the change in forced expiratory volume in the first second (FEV1) and FEV1/FVC over time. As secondary outcome we investigated sex, smoking, enzyme replacement therapy (ERT), residual enzyme activity, and Mainz Severity Score Index as possible predictors.95 patients (41% male, 38.2 ± 14.5 years) were included. The overall prevalence of bronchial obstruction (BO, (FEV1/FVC < 70%)) was 46%, with male sex, age and smoking as significant predictors. FEV1 decreased 29 ml per year (95% CI -36, -22 ml, p<0.0001). FEV1 decline was significantly higher in males (p = 0.009) and in patients on ERT (p = 0.004). Conclusion: Pulmonary involvement seems to be a relevant manifestation of Fabry disease, and routine PFTs should therefore be included in the multidisciplinary follow-up of these patients.

SUBMITTER: Franzen DP

PROVIDER: S-EPMC5526574 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

Franzen Daniel P DP Nowak Albina A Haile Sarah R SR Mottet Dominique D Bonani Marco M Dormond Olivier O Kohler Malcolm M Krayenbuehl Pierre A PA Barbey Frederic F

PloS one 20170725 7

<h4>Introduction</h4>Fabry disease (FD) is a lysosomal storage disorder leading to decreased α-galactosidase A enzyme activity and subsequent abnormal accumulation of glycosphingolipids in various organs. Although histological evidence of lung involvement has been demonstrated, the functional impact of these changes is less clear.<h4>Materials and methods</h4>Adult patients with FD who had yearly pulmonary function tests (PFT) at two centers from 1999 thru 2015 were eligible for this observation ...[more]

PMID: 28742806

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Project description:This study aimed to evaluate audiological and vestibular involvement in Fabry disease and the effects of enzyme replacement therapy with human alpha-galactosidase A. The study population comprised 20 patients (11 males, 9 females) aged 15-69 years (mean 39.7). Patients underwent a complete clinical and instrumental evaluation before starting and during enzyme replacement therapy. Median follow-up was 51.5 months (range 25-73). Nine patients (45%) complained of hearing symptoms (hearing loss, tinnitus); for six of them the onset and/or progression of the hearing loss were sudden. Vertigo or dizziness was reported by 6 patients (30%). Audiological evaluation showed a sensorineural hearing loss in 18 ears (45%; 10 in male patients, 8 in females). The hearing thresholds for 0.5, 1, 2 and 4 kHz frequencies ranged from 10 to 65 dB HL. Hearing loss was unilateral in 8 cases (40%; 4 in male patients, 4 in females). Also high frequency hearing loss for 4 and 8 kHz was evaluated. No signs of retro-cochlear lesions were observed by means of otoacoustic emissions and auditory brainstem response. Vestibular examinations showed a functional impairment in 7 ears (17.5%, all male patients). During enzyme replacement therapy the auditory function showed some degrees of worsening but no significant changes were observed at statistical analysis. In conclusion involvement of the inner ear is common in men and women with Fabry disease. In this study, a high incidence of cochlear hearing loss was found, which was typically unilateral and showed onset and/or progression by sudden episodes. Vascular or hydropic mechanisms could be hypothesized to explain audiological findings. Vestibular involvement showed a lower incidence and different pattern, thus suggesting that several patho-physiological mechanisms could play a role in determining inner ear damage in Fabry disease. Results obtained show that enzyme replacement therapy may stabilize hearing function; however, further studies on the physiopathology of the inner ear damage are needed.

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Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

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Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

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