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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.
Journal of Inherited Metabolic Disease 11/2007; 30(5):790-9. · 3.58 Impact Factor
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D. Karetova,
J. Bultas,
A. Linhart,
J.C. Lubanda, S. Magage,
P. Uklikova,
T. Palecek,
J. Ledvinova,
H. Poupetova,
R. Dobrovolny,
M. Hrebicek,
M. Elleder
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ABSTRACT: Background: The severity of organ impairment in heterozygous females with Fabry disease may be as serious as in males. It has been repeatedly shown that the incidence of affected organs increases with age and comes one decade later than in males. Besides age, the process of X inactivation also has an important influence. The ratio between inactivated normal and defective chromosomes could influence the level of the key enzyme: α-galactosidase A. We have tried to prove this hypothesis.Methods and Results: Analysis of this relationship was carried out in a cohort of 54 heterozygous females (average age, 41.2 years) from 16 families. Diagnosis of Fabry disease was based on the identification of a chromosomal defect. We used the Mainz Severity Score Index to evaluate the extent of disease. To clarify the relationship between levels of α-galactosidase A in leukocytes, age and organ impairment, we conducted multivariant analysis. The correlation coefficients were highly significant for age (r = 0.5765, p < 0.0001) and for α-galactosidase A activity (r = − 0.4856, p < 0.05). For better demonstration of the relationship, the cohort of women was divided into tertiles according to age and α-galactosidase A activity in leukocytes (Figure 1).Figure 1. Correlation between the Mainz Severity Score Index (MSSI), age and α-galactosidase A activity in leukocytes (nmol/h/mg) in females with Fabry diseaseDownload figure to PowerPointConclusion: From the presented graph and correlation analysis it is clear that, in addition to age, the level of α-galactosidase A in leukocytes is also an important predictor of the degree of organ involvement in heterozygous females with Fabry disease.
Acta Paediatrica 01/2007; 95(S451):124 - 128. · 2.07 Impact Factor
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ABSTRACT: Fabry's disease is a rare lysosomal storage disease caused by the X-linked defect of the enzyme alpha-galactosidase A leading to the intracellular accumulation of glycosphingolipids in various organs and tissues. Cardiac involvement is frequent and, in individuals with some residual enzyme activity, may be the sole manifestation of the disease. Hemizygous men are generally more seriously affected than heterozygous women. The dominant cardiac manifestations include myocardial hypertrophy of the left ventricle, which, in some patients, mimics hypertrophic cardiomypathy. Left ventricular systolic function is usually preserved, on the other hand mild to moderate diastolic dysfunction is regularly detected. Valvular abnormalities are frequently noted. However, hemodynamically significant lesions are rare. Conduction system involvement leads initially to the shortening of atrioventricular conduction, in later stages, with a progression of the disease, antrioventricular blocks and various forms of supraventricular and ventricular arrhythmias appear. Myocardial ischemia in Fabry disease has in most cases a functional origin due to endothelial dysfunction of coronary arteries and also due to the increase oxygen demand of hypertrophied myocardium. The results of so far performed studies with enzyme replacement therapy are promising in preventing further deterioration and even improving function of affected organs.
Vnitr̆ní lékar̆ství 12/2004; 50(11):846-51.
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ABSTRACT: Fabry disease is a rare X-linked defect of the lysosomal enzyme alpha-galactosidase A. The disease is characterized by progressive intracellular accumulation of neutral glycosphingolipids. The storage occurs within various tissues and cells, including cardiocytes, the cardiac conduction system, and valvular fibrocytes. Cardiac involvement may be the sole manifestation of the disease, particularly in individuals with residual enzyme activity. In general, hemizygous men are more seriously affected than heterozygous women. The main cardiac manifestations include myocardial hypertrophy, which, in some patients, mimics hypertrophic cardiomyopathy. Conduction system involvement leads to PR shortening or, in later stages, to AV blocks. Arrhythmias presenting with variable severity also appear to be common. Valvular involvement is frequently noted but generally mild and clinically non-significant. Newly available enzyme replacement therapy has produced promising results in preventing further functional deterioration of affected organs and possibly also in reversing impaired function. CONCLUSIONS: With the advent of effective enzyme replacement therapy, early diagnosis of Fabry disease may be crucial for patient prognosis.
Acta paediatrica (Oslo, Norway: 1992). Supplement 02/2002; 91(439):15-20.
