Natural history of the respiratory involvement in Anderson-Fabry disease.

Second Department of Internal Medicine, Charles University in Prague, First Faculty of Medicine, U Nemocnice 2, 128 08, Prague 2, Czech Republic.
Journal of Inherited Metabolic Disease (Impact Factor: 4.14). 11/2007; 30(5):790-9. DOI: 10.1007/s10545-007-0616-9
Source: PubMed

ABSTRACT Anderson-Fabry disease (AFD) is an X-linked disorder caused by deficient activity of enzyme alpha-galactosidase A, resulting in the accumulation of glycosphingolipids within lysosomes. Pulmonary involvement in AFD has previously been documented, but until now has been studied only in a few series of patients without any longitudinal follow-up. The aim of this study was to compare spirometric changes in AFD patients with a matched control population and to follow the subsequent progression of the disease.
Fifty individuals (27 women, 23 men, mean age 40 +/- 14 years) with AFD from 14 families underwent a static spirometric examination under standard conditions. A set of indices was compared with that of the control population. Out of this cohort, 39 individuals not receiving enzyme replacement therapy were longitudinally evaluated (median follow-up time 24 months).
A clinically significant reduction in spirometric parameters, corresponding to mild to severe airway obstruction, was observed in 26% of women and 61% of men. During the serial follow-up, a significant (p < 0.05) age-dependent reduction of predicted %FVC and %FEV1 values was observed in male patients, while the influence of age was not seen in female patients. The %FEF(25-75) values decreased by similar degrees in men and women and in older and younger patients, indicating that progressive bronchial disease affects the small airways first.
We have demonstrated a clinically relevant age- and sex-dependent progressive pulmonary involvement in AFD patients. The effects of enzyme replacement therapy on pulmonary involvement remain to be demonstrated.

  • Value in Health 05/2010; 13(3). · 2.89 Impact Factor
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    ABSTRACT: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A, which leads to storage of sphingolipids in virtually all human cells and consequently to organ dysfunction. Pulmonary involvement is still debated. But, obstructive lung disease is up to ten times more prevalent in patients with FD compared to general public. Also, an accelerated decline in forced expiratory volume in one second (FEV1) over time was observed in these patients. Lysosomal storage of glycosphingolipids is considered leading to small airway disease via hyperplasia of the bronchiolar smooth muscle cells. Larger airways may become involved with ongoing disease process. There is no evidence for involvement of the lung interstitium in FD. The effect of enzyme replacement therapy on respiratory involvement remains to be determined in large, prospective controlled trials.
    European Journal of Internal Medicine 05/2013; · 2.30 Impact Factor
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    ABSTRACT: Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the GLA gene, which leads to a deficiency in α-galactosidase A. The abnormal accumulation of glycosphingolipids, primarily globotriaosylceramide, manifests as serious and progressive impairment of renal and cardiac function. In addition, patients experience pain, gastrointestinal disturbance, transient ischemic attacks and strokes. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic. This review covers all basic aspects of the disease such as epidemiology, pathophysiology, clinical presentation by systems, diagnosis, management, prevention, and repercussions on quality of life. With the development of enzyme replacement therapy in the past few years, early initiation of treatment was found to be key for reduction of disease burden in major affected organs with improvement in neuropathic pain, decreased cardiac mass and stabilization of renal function, gastrointestinal symptoms, and hearing. This review aims to raise the awareness of the signs and symptoms of Fabry disease as well as to provide guidelines for the diagnosis and treatment.
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