Natural history of the respiratory involvement in Anderson-Fabry disease

Charles University in Prague, Praha, Praha, Czech Republic
Journal of Inherited Metabolic Disease (Impact Factor: 3.37). 11/2007; 30(5):790-9. DOI: 10.1007/s10545-007-0616-9
Source: PubMed


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.

11 Reads
  • Source
    • "Although obstructive lung disease, mainly of the small airway system, is a common pathological finding in Fabry disease [2] [3] [4] [5], pulmonary involvement is not widely appreciated by clinicians. Respiratory symptoms may be falsely interpreted as arising from cardiac dysfunction [6], and lung failure due to Fabry disease has not been reported so far. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction. Fabry disease is a rare X-linked lysosomal storage disorder, characterized by an α-galactosidase A deficiency resulting in globotriaosylceramide storage within cells. Subsequently, various organ systems are involved, clinically the most important are kidneys, the heart, and the peripheral and central nervous systems. Although obstructive lung disease is a common pathological finding in Fabry disease, pulmonary involvement is a clinically disregarded feature. Case Presentation. We report a patient with a diagnosis of chronic obstructive pulmonary disease (COPD) who received a single lung transplant in 2007. Later, a kidney biopsy revealed the diagnosis of Fabry disease, which was confirmed by enzymatic and genetic testing. Ultrastructural changes in a native lung biopsy were consistent with the diagnosis. Although the association of a lung transplant and Fabry disease appears far-fetched on first sight, respiratory impairment cannot be denied in Fabry disease. Conclusion. With this case presentation, we would like to stimulate discussion about rare differential diagnoses hidden beneath widespread disease and that a correct diagnosis is the base of an optimal treatment strategy for each patient. Overall, the patient might have benefited from specific enzyme replacement therapy, especially in view of the chronic kidney disease.
    04/2013; 2013:905743. DOI:10.1155/2013/905743
  • Source
    • "Treadmill cardiopulmonary exercise testing demonstrates reduction in maximal oxygen consumption compared with normal controls (Bierer et al 2005). Although hemizygous men tend to be more severely affected, both hemizygotes and heterozygotes experience gradual deterioration in pulmonary function with age (Magage et al 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fabry disease is an X-linked glycosphingolipidosis caused by a deficiency of α-galactosidase A, a lysosomal enzyme. Symptoms in hemizygous males and heterozygous females are due to lysosomal storage of globotriaosylceramide in the central and peripheral nervous system, vascular endothelium, cardiac valves and myocytes, gastrointestinal tract, and renal epithelium. Pulmonary involvement is also a recognized manifestation of Fabry disease, but histopathological evidence of pulmonary lysosomal storage is scant. We report a 51-year-old woman with a G43R α-galactosidase A mutation and normal spirometry testing 2.5 years prior to presentation, who experienced a dry, nonproductive cough that persisted despite treatment with antibiotics and bronchodilators. Spirometry demonstrated a mixed restrictive/obstructive pattern as well as impaired gas exchange. Patchy ground-glass pulmonary interstitial infiltrates were found on plain radiography and computerized tomography. She underwent an open lung biopsy that demonstrated peribronchiolar fibrosis and smooth-muscle hyperplasia. Prominent inclusion bodies of the bronchiolar/arteriolar smooth muscle and endothelium were present. Electron microscopy indicated the inclusion bodies were lamellated zebra bodies consistent with globotriaosylceramide storage. Enzyme replacement therapy (ERT) with agalsidase-beta was instituted. Since initiation of therapy, she occasionally has a dry cough but markers of obstructive lung disease have remained stable in the past 4 years. This report demonstrates that pulmonary involvement in Fabry disease is due to lysosomal storage, and suggests that ERT is capable of stabilizing pulmonary Fabry disease. However, progressive worsening of her total lung capacity indicates that ERT cannot reverse the ongoing process of fibrosis also seen in Fabry disease.
    Journal of Inherited Metabolic Disease 11/2008; 31 Suppl 2(2, supplement):S369-74. DOI:10.1007/s10545-008-0930-x · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 20-year-old man presented with generalized acquired anhidrosis and heat intolerance which was confirmed by a sweat test. Other clinical features included severe pain of the extremities and cutaneous angiokeratomas. On electronmicroscopy, granules specific for Fabry's disease were observed in the endothelial cells. Biochemical examination revealed a decreased level of serum alpha-galactosidase A. These findings confirmed the diagnosis of Fabry's disease.
    Internal Medicine 06/1992; 31(5):682-5. DOI:10.2169/internalmedicine.31.682 · 0.90 Impact Factor
Show more