J Cardiovasc Ultrasound.  2016 Dec;24(4):324-328. 10.4250/jcu.2016.24.4.324.

Fabry Disease Presenting with Hypertrophic Cardiomyopathy and Tricuspid Regurgitation

• Cho SC
• Yoo HW
• Lee JW
• Jang JY
• Heo R
• Song JM

• KMID: 2364651
• DOI: http://doi.org/10.4250/jcu.2016.24.4.324

Abstract

A 71-year-old female who was diagnosed with nonobstructive hypertrophic cardiomyopathy since 1999 presented with dyspnea and severe edema on both legs. For the management of her symptom, cardiac surgery including tricuspid annuloplasty, Maze operation and right atrial reduction plasty was performed. During follow-up after cardiac surgery, a plasma α-galactosidase activity was checked for the screening of Fabry disease and the result was around lower normal limit. DNA analysis was implemented for confirmation and it revealed a heterozygote α-galactosidase mutation at exon 6 [c.901C>T (p.Arg301Ter)]. This case suggests that Fabry disease might be easily undetected, and clinical suspicion is critical.

Keyword

Fabry disease; Hypertrophic cardiomyopathy; Tricuspid regurgitation

MeSH Terms

Aged
Cardiomyopathy, Hypertrophic*
DNA
Dyspnea
Edema
Exons
Fabry Disease*
Female
Follow-Up Studies
Heterozygote
Humans
Leg
Mass Screening
Plasma
Thoracic Surgery
Tricuspid Valve Insufficiency*
DNA

Figure

• 

  Fig. 1 Electrocardiogram shows atrial fibrillation and ST-T change with a mean ventricular rate of 56 bpm.

• 

  Fig. 2 Transthoracic echocardiography shows a markedly thickened wall of left ventricle with a high echo density (A) and severe tricuspid regurgitation (B).

• 

  Fig. 3 Cardiac magnetic resonance image shows a fuzzy delayed Gadolinium enhancement at the mid anterolateral and inferolateral myocardium of the left ventricle (arrow).

• 

  Fig. 4 Histology shows a diffuse vacuolization of myocytes (arrow) causing large clear spaces in the myocardial cells and lateralization of nucleus (hematoxylin and eosin, × 200).

• 

  Fig. 5 Automated sequencing profile of genomic DNA reveals a heterozygote α-galactosidase A mutation at exon 6 [c.901C>T (p.Arg301Ter)].

• 

  Fig. 6 Slit lamp examination shows corneal opacity and severe corneal verticillata (arrow).

• 

  Fig. 7 Audiogram shows bilateral sensorineural hearing loss. Bone conduction loss is noted above 4 kHz.

Reference

1. Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001; 285:2743–2749.

2. Nakao S, Takenaka T, Maeda M, Kodama C, Tanaka A, Tahara M, Yoshida A, Kuriyama M, Hayashibe H, Sakuraba H, Tanaka H. An atypical variant of Fabry's disease in men with left ventricular hypertrophy. N Engl J Med. 1995; 333:288–293.

3. Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, Maseri A, Frustaci A. Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation. 2004; 110:1047–1053.

4. Kampmann C, Baehner F, Whybra C, Martin C, Wiethoff CM, Ries M, Gal A, Beck M. Cardiac manifestations of Anderson-Fabry disease in heterozygous females. J Am Coll Cardiol. 2002; 40:1668–1674.

5. Desnick RJ, Brady RO. Fabry disease in childhood. J Pediatr. 2004; 144:5 Suppl. S20–S26.

6. Linhart A, Palecek T, Bultas J, Ferguson JJ, Hrudová J, Karetová D, Zeman J, Ledvinová J, Poupetová H, Elleder M, Aschermann M. New insights in cardiac structural changes in patients with Fabry's disease. Am Heart J. 2000; 139:1101–1108.

7. Weidemann F, Breunig F, Beer M, Sandstede J, Störk S, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM. The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J. 2005; 26:1221–1227.

8. Pieroni M, Chimenti C, De Cobelli F, Morgante E, Del Maschio A, Gaudio C, Russo MA, Frustaci A. Fabry's disease cardiomyopathy: echocardiographic detection of endomyocardial glycosphingolipid compartmentalization. J Am Coll Cardiol. 2006; 47:1663–1671.

9. Pieroni M, Chimenti C, Ricci R, Sale P, Russo MA, Frustaci A. Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation. 2003; 107:1978–1984.

10. Toro R, Perez-Isla L, Doxastaquis G, Barba MA, Gallego AR, Pintos G, Barbados FJ, Mangas A, Zamorano JL. Clinical usefulness of tissue Doppler imaging in predicting preclinical Fabry cardiomyopathy. Int J Cardiol. 2009; 132:38–44.

11. Moon JC, Sachdev B, Elkington AG, McKenna WJ, Mehta A, Pennell DJ, Leed PJ, Elliott PM. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium. Eur Heart J. 2003; 24:2151–2155.

12. Koitabashi N, Utsugi T, Seki R, Okamoto E, Sando Y, Kaneko Y, Nagai R. Biopsy-proven cardiomyopathy in heterozygous Fabry's disease. Jpn Circ J. 1999; 63:572–575.

13. Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study. Circulation. 2003; 108:1299–1301.

14. Koskenvuo JW, Hartiala JJ, Nuutila P, Kalliokoski R, Viikari JS, Engblom E, Penttinen M, Knuuti J, Mononen I, Kantola IM. Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters. J Inherit Metab Dis. 2008; 31:432–441.

15. Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ. 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.