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Thoracic Aortic Dilation/Aneurysm in Fabry Disease

      To the Editor:
      We read with great interest the review of Paterick et al entitled “Aortopathies: Etiologies, Genetics, Differential Diagnosis, Prognosis and Management.”
      • Paterick T.E.
      • Humphries J.A.
      • Ammar K.A.
      • et al.
      Aortopathies: etiologies, genetics, differential diagnosis, prognosis and management.
      The authors discuss in part the differential diagnoses of ascending aortic aneurysm. We were, however, surprised that Fabry disease was not considered in the list of genetic diseases associated with ascending aortic dilation/aneurysm.
      Fabry disease is an X-linked recessive disorder that is caused by deficiency of the lysosomal enzyme α-galactosidase A. As a result, globotriaosylceramide accumulates in almost all cells and tissues. The major structural change observed in the wall of the arterial tree of Fabry patients is an abnormal increased intima-media thickness due mainly to hypertrophy and hyperplasia of the vascular smooth-muscle cells; which mechanism remains unclear. Interestingly, this arterial remodeling is not related to hypertension, intramural inflammation, or atherosclerosis.
      Vessel dilation is a common finding in Fabry disease, in particular in the basilar trunk and ascending aorta. Previous echocardiographic studies in small groups of patients have reported aortic root dilation in 30%-56% of males, although the criteria used to determine dilation varied.
      • Linhart A.
      • Palecek T.
      • Bultas J.
      • et al.
      New insights in cardiac structural changes inpatients with Fabry's disease.
      • Goldman M.E.
      • Cantor R.
      • Schwartz M.F.
      • et al.
      Echocardiographic abnormalities and disease severity in Fabry's disease.
      • Bass J.L.
      • Shrivastava S.
      • Grabowski G.A.
      • et al.
      The M-mode echocardiogram in Fabry's disease.
      In a recent study we have shown, using echocardiograms and cardiovascular magnetic resonance imaging, a high prevalence of asymptomatic ascending aorta dilation and aneurysm in male patients with Fabry disease compared to the normal population.
      • Barbey F.
      • Qanadli S.D.
      • Juli C.
      • et al.
      Aortic remodelling in Fabry disease.
      At the level of the sinus of Valsalva and ascending aorta, a dilation was present in 32.7% and 29.6% of 52 male patients (mean age 39.9 ± 11.7 years), respectively. Fusiform aneurysms involving the aortic root or ascending aorta were found in 9.6% of male patients, that is, at a younger age compared with the general population. Gender and age were strongly associated with dilation. To date, there is no reported case of dissection of the ascending aorta in a Fabry patient, possibly because the disease remains underdiagnosed.
      Thus, in our opinion, Fabry disease should definitively be included in the differential diagnoses of genetic diseases leading to premature ascending aortic dilation/aneurysm.

      References

        • Paterick T.E.
        • Humphries J.A.
        • Ammar K.A.
        • et al.
        Aortopathies: etiologies, genetics, differential diagnosis, prognosis and management.
        Am J Med. 2013; 126: 670-678
        • Linhart A.
        • Palecek T.
        • Bultas J.
        • et al.
        New insights in cardiac structural changes inpatients with Fabry's disease.
        Am Heart J. 2000; 139: 1101-1108
        • Goldman M.E.
        • Cantor R.
        • Schwartz M.F.
        • et al.
        Echocardiographic abnormalities and disease severity in Fabry's disease.
        J Am Coll Cardiol. 1986; 7: 1157-1161
        • Bass J.L.
        • Shrivastava S.
        • Grabowski G.A.
        • et al.
        The M-mode echocardiogram in Fabry's disease.
        Am Heart J. 1980; 100: 807-812
        • Barbey F.
        • Qanadli S.D.
        • Juli C.
        • et al.
        Aortic remodelling in Fabry disease.
        Eur Heart J. 2010; 31: 347-353

      Linked Article

      • Aortopathies: Etiologies, Genetics, Differential Diagnosis, Prognosis and Management
        The American Journal of MedicineVol. 126Issue 8
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          Aortic root and ascending aortic dilatation are indicators associated with risk of aortic dissection, which varies according to underlying etiologic associations, indexed aortic root size, and rate of progression. Typical aortic involvement is most commonly seen in syndromic cases for which there is increasing evidence that aortic aneurysm represents a spectrum of familial inheritance associated with variable genetic penetrance and phenotypic expression. Aortic root and ascending aortic dimensions should be measured routinely with echocardiography.
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      • The Reply
        The American Journal of MedicineVol. 126Issue 12
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          We appreciate the letter to the editor by Dormond et al (“Thoracic Aortic Dilation/Aneurysm in Fabry Disease”)1 written in response to our review, “Aortopathies: Etiologies, Genetics, Differential Diagnosis, Prognosis and Management.”2 They bring to our attention an evolving finding in a recent work by Barbey et al3 highlighting the association between Fabry disease and aortic dilation/aneurysm. The association deserves continued study to better define the pathophysiologic mechanisms leading to aortic dilation/aneurysm.
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