Arterial remodelling in Fabry disease

Boutouyrie, Pierre; Laurent, Stéphane; Laloux, B; Lidove, O; Grunfeld, J.P; Germain, Dominique P.

doi:10.1080/080352502762457950

Cited by 18 publications

(27 citation statements)

References 18 publications

(31 reference statements)

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“…However, the slope was 2.3-fold higher in FD patients than in controls (p < 0.001). Common carotid artery (CCA) IMT was mildly but significantly increased in patients with FD (+18%), whereas distensibility was unchanged [164,165]. …”

Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,025

1,230

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.

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Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,025

1,230

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“…An investigation by Barbey and co-workers provided evidence for the presence of an unidentified substance in plasma of symptomatic Fabry disease patients that stimulates proliferation of vascular smooth-muscle cells and cardiomyocytes in vitro (Barbey et al 2006a). It is conceivable that this substance is a causative factor in the development of left ventricular hypertrophy and increased intima media thickness in Fabry patients (Boutouyrie et al 2002; Barbey et al 2006b; Kalliokoski et al 2006; Vedder et al 2007b; Rombach et al 2010b). …”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies

Aerts

Kallemeijn

Wegdam

et al. 2011

J of Inher Metab Disea

101

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A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, recently developed chemical tools allowing specific visualization of enzymatically active lysosomal glucocerebrosidase are described. Such probes, coined inhibodies, offer entirely new possibilities for more sophisticated molecular diagnosis, enzyme replacement therapy monitoring, and fundamental research.

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“…In peripheral arteries, enhanced endothelium-dependent vasodilatation was shown in one study (Altarescu et al 2001), but no significant changes in another (Kalliokoski et al 2005). In addition, studies have shown structural changes in peripheral arteries, such as increased arterial wall thickness and distensibility (Boutouyrie et al 2002). Fabry disease also causes changes in coronary vascular function.…”

Section: Introductionmentioning

confidence: 96%

The effect of 12‐month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease

Kalliokoski

Kantola

Kalliokoski

et al. 2006

J of Inher Metab Disea

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Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

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Arterial remodelling in Fabry disease

Cited by 18 publications

References 18 publications

Fabry disease

Fabry disease

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies

The effect of 12‐month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease

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