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European Journal of Echocardiography Advance Access originally published online on April 4, 2008
European Journal of Echocardiography 2008 9(5):697-699; doi:10.1093/ejechocard/jen132
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Fabry's disease presenting as ventricular tachycardia and Left Ventricular ‘Hypertrophy’

Subodh B. Joshi1,*, Walid Ahmar2, Geoff Lee3 and Anuradha Aggarwal3

1 Washington Hospital Center, 110 Irving St. NW, Washington, DC 20010, USA
2 Monash Medical Centre, Clayton, Australia
3 Royal Melbourne Hospital, Parkville, Australia

Received 26 November 2007; accepted after revision 2 March 2008; online publish-ahead-of-print 4 April 2008.

* Corresponding author. Tel: +1 202 441 8717; fax: +1 202 877 0011. E-mail address: subodh.joshi{at}gmail.com


   Abstract
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 Abstract
Case record
 Discussion
 References
 
Fabry’s disease (FD) is a genetic disorder leading to deficiency of {alpha}-galactosidase A. Enzymatic replacement therapy has recently become available. Patients with classical FD develop multi-system involvement; however, there is an increasingly recognized cardiac variant that presents as unexplained left ventricular hypertrophy. We describe a patient with Fabry's disease who presented with ventricular tachycardia.

Keywords: Fabry's; Ventricular tachycardia; Sudden cardiac death; Left ventricular hypertrophy


   Case record
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A 57-year-old man was admitted to hospital after surviving an out-of-hospital cardiac arrest. The patient had suddenly collapsed, with no preceding palpitations, chest pain, or dizziness. Electrocardiographic monitoring revealed a broad complex tachycardia, which reverted with a single DC shock. The past medical history included atrial fibrillation treated with digoxin and warfarin.

On examination in the emergency department, the patient was in atrial fibrillation with a heart rate of 100 bpm and a blood pressure of 125/85. There were two normal heart sounds and no signs of congestive heart failure. A 12-lead surface electrocardiograph showed atrial fibrillation with a left bundle branch block. Cardiac biomarkers were elevated with a creatinine kinase of 470 IU/L and troponin I of 3.3 µg/L. The international normalized ratio (INR) was elevated at 3.2, and the serum creatinine and urea were normal. An amiodarone infusion was commenced.

A transthoracic echocardiogram showed a mildly dilated left ventricle with global dysfunction. Increased thickness of both the left and right ventricular walls was noted (Figure 1).


Figure 1
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  		Figure 1 Echocardiogram—increased left and right ventricular wall thickness.

 
Coronary angiography was normal. (Provocative tests for vasospasm were not performed.) An implantable cardioverter-defibrillator was placed.

Given the increased biventricular wall thickness, a trans-venous myocardial biopsy was performed. Electron microscopy revealed abundant cytoplasmic myelinosomes and mitochondria containing lamellated ‘zebra bodies’, consistent with Fabry's disease (Figure 2). The diagnosis was confirmed with demonstration of a low-plasma {alpha}-galactosidase level and further characteristic changes on renal biopsy. There was no family history of Fabry’s disease (FD) and no extra-cardiac manifestations of the condition were apparent. Enzyme replacement therapy was initiated.


Figure 2
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  		Figure 2 Electromicroscopy—cytoplasmic myelinosomes and mitochondria containing lamellated ‘zebra bodies’.

 

   Discussion
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 Abstract
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 Discussion
References
 
Fabry’s disease is an X-linked lyposomal storage disorder as a result of deficiency in the enzyme {alpha}-galactosidase A. It is found in all ethnic groups and predominately affects males; however, females can be affected because of random X chromosomal inactivation.1,2 Clinical manifestations are as a result of the accumulation of globotriaosylceramide, particularly in the vascular endothelium, leading to small vessel ischaemia. The classical phenotype occurs in males with undetectable or very low levels of {alpha}-galactosidase activity resulting in severe renal, cerebrovascular, and cardiac disease. End-stage renal failure supervenes during adulthood, and it is estimated that FD accounts for 1.2% of the dialysis population.3 Cardiac manifestations include left ventricular hypertrophy, ascending aorta dilatation, minor structural changes in cardiac valves,4 a shortened PR interval,5 and conduction system disease predisposing to bradyarrhythmmias.6 Tachyrrhythmias occur commonly in patients with FD, and there may be an increased risk of sudden death.7

Recently, there has been increasing recognition of an atypical cardiac variant of FD.8 Patients have residual low levels of {alpha}-galactosidase A activity that prevents the development of the non-cardiac sequalae. The disease presents in middle age as unexplained left ventricular hypertrophy. One study found the incidence of FD to be as high as 3% in males with left ventricular hypertrophy.9 Among patients diagnosed with late onset hypertrophic cardiomyopathy, as many as 6% of men and 12% of women may be affected by FD.10,11 Although asymmetric hypertrophy can occur, the likelihood of FD is greatest in the normotensive patient with concentric left ventricular hypertrophy.10 The incidence of FD is extremely low in patients with outflow tract obstruction severe enough to warrant myomectomy.12 With time, there is progressive fibrosis within the myocardium and deterioration in left ventricular function.7 Eventually, this may progress to a dilated cardiomyopathy and predispose to serious ventricular arrhythmmias.13

The diagnosis of FD is now of greater importance because of the availability of enzymatic replacement therapy (ERT). Although mortality data are lacking, enzyme treatment has been shown to clear microvascular endothelial deposits of globotriaosylceramide.14 ERT has been shown to reduce left ventricular wall thickness and mass and improve regional myocardial function.15 Dramatic improvement with ERT has been reported in patients with severe left ventricular dysfunction.16

In males, FD is readily diagnosed by very low levels of {alpha}-galactosidase A in the peripheral blood.1 The sensitivity is substantially lower in females who have higher levels of residual {alpha}-Gal A activity.1 Genetic testing confirms the diagnosis by demonstration of a mutation in the {alpha}-Gal A gene on the long arm of the X chromosome.1 Endomyocardial biopsy may also be used, which typically shows concentric lamellar glycolipid deposition on electron microscopy.11 Recently, characteristic echocardiographic features have been described consisting of a binary appearance of the left ventricular wall as a result of glycosphingolipid compartmentalization (not present in the patient described in the case record).17 Reduction in tissue-Doppler velocities, reflecting diastolic dysfunction, can be detected earlier in the disease process, but are not specific to FD18. On magnetic resonance imaging, focal areas of late enhancement after gadolinium administration are seen but the specificity for FD remains unclear.19 The late enhancement reflects myocardial fibrosis and its extent may predict the lack of response to therapy.20

The availability of specific therapy for FD makes its identification of great importance. In addition to those patients with classical multi-system involvement, the disease should be considered in patients presenting with unexplained increased ventricular wall thickness.

Conflict of interest: none declared.


   References
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 Abstract
 Case record
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  1. Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med (2003) 138:338–46.[Abstract/Free Full Text]
  2. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA (1999) 281:249–54.[Abstract/Free Full Text]
  3. Nakao S, Kodama C, Takenaka T, Tanaka A, Yasumoto Y, Yoshida A, et al. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a ‘renal variant’ phenotype. Kidney Int (2003) 64:801–7.[CrossRef][Web of Science][Medline]
  4. Linhart A, Palecek T, Bultas J, et al. New insights in cardiac structural changes in patients with Fabry’s disease. Am Heart J (2000) 139:1101–8.[CrossRef][Web of Science][Medline]
  5. Roudebush CP, Foerster JM, Bing OH. The abbreviated PR interval of Fabry’s disease. N Engl J Med (1973) 289:357–8.[Web of Science][Medline]
  6. Kampmann C, Baehner F, Ries M, Beck M. Cardiac involvement in Anderson-Fabry disease (review). J Am Soc Nephrol (2002) 13:S147–S149.[Free Full Text]
  7. Shah JS, Hughes DA, Sachdev B, Tome M, Ward D, Lee P, et al. Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease. Am J Cardiol (2005) 96:842–6.[CrossRef][Web of Science][Medline]
  8. von Scheidt W, Eng CM, Fitzmaurice TF, Erdmann E, Hubner G, Olsen EG, et al. An atypical variant of Fabry’s disease with manifestations confined to the myocardium. N Engl J Med (1991) 324:395–9.[Web of Science][Medline]
  9. Nakao S, Takenaka T, Maeda M, et al. An atypical variant of Fabry’s disease in men with left ventricular hypertrophy. N Engl J Med (1995) 333:288–93.[Abstract/Free Full Text]
  10. Sachdev B, Takenaka T, Teraguchi H, et al. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation (2002) 105:1407–11.[Abstract/Free Full Text]
  11. Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, et al. Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation (2004) 110:1047–53.[Abstract/Free Full Text]
  12. Ommen SR, Nishimura RA, Edwards WD. Fabry disease: a mimic for obstructive hypertrophic cardiomyopathy? Heart (2003) 89:929–30.[Free Full Text]
  13. Igawa O, Miake J, Hisatome I. Ventricular tachycardias and dilated cardiomyopathy caused by Fabry disease. Pacing Clin Electrophysiol (2005) 28:1142.[CrossRef][Medline]
  14. Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, et al, International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A-replacement therapy in Fabry’s disease. N Engl J Med (2001) 345:9–16.[Abstract/Free Full Text]
  15. Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, et al. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation (2003) 108:1299–301.[Abstract/Free Full Text]
  16. Frustaci A, Chimenti C, Ricci R, Natale L, Russo MA, Pieroni M, et al. Improvement in cardiac function in the cardiac variant of Fabry’s disease with galactose-infusion therapy. N Engl J Med (2001) 345:25–32.[Free Full Text]
  17. Pieroni M, Chimenti C, De Cobelli F, Morgante E, Del Maschio A, Gaudio C, et al. Fabry’s disease cardiomyopathy: echocardiographic detection of endomyocardial glycosphingolipid compartmentalization. J Am Coll Cardiol (2006) 47:1663–71.[Abstract/Free Full Text]
  18. Pieroni M, Chimenti C, Ricci R, Sale P, Russo MA, Frustaci A. Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation (2003) 107:1978–84.[Abstract/Free Full Text]
  19. Moon JC, Sachdev B, Elkington AG, McKenna WJ, Mehta A, Pennell DJ, et al. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J (2003) 24:2151–5.[Abstract/Free Full Text]
  20. Beer M, Weidemann F, Breunig F, Knoll A, Koeppe S, Machann W, et al. Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry’s cardiomyopathy. Am J Cardiol (2006) 97:1515–8.[CrossRef][Web of Science][Medline]

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