Die Fabry-Kardiomyopathie als Differenzialdiagnose des akuten Koronarsyndroms

Abstract

The progressive cardiomyopathy in patients with Fabry disease is often accompanied by angina pectoris and elevated levels of high-sensitive troponin T (hs-TnT), potentially mimicking acute coronary syndrome. Here, we present to representative cases with focus on clinical, diagnostic and therapeutic settings. An overview on the cardiomyopathy associated with Fabry disease and its role as differential diagnosis of acute coronary syndrome is provided. Fabry cardiomyopathy might exhibit similar clinical and biochemical constellations as seen in acute coronary syndrome. Thus, Fabry cardiomyopathy should be considered a differential diagnosis in acute coronary syndrome, particularly in patients demonstrating left ventricular hypertrophy of unknown origin.

Erhöhte Troponin-Werte im Serum sind häufig Ausdruck eines akuten Koronarsyndroms. Allerdings kommen differenzialdiagnostisch auch zahlreiche weitere Pathologien in Betracht. Dazu gehören angeborene und erworbene Kardiomyopathien, die spätestens nach Ausschluss eines akuten Koronarsyndroms weiter abgeklärt bzw. ausgeschlossen werden sollten. Die erhöhten Werte können auch auf eine kardiale Beteiligung bei Morbus Fabry hinweisen. Aufgrund der Seltenheit der Erkrankung wird diese oftmals zunächst nicht erkannt, sodass eine spezifische kausale Therapie ausbleibt oder erst im Spätstadium der Erkrankung initiiert wird.

Schlüsselwörter

Akutes Koronarsyndrom - Fabry Kardiomyopathie - Troponin - Hypertrophe Kardiomyopathie - Lysosomale Speicherkrankheit - Myokardinfarkt

Key words

acute coronary syndrome - fabry cardiomyopathy - troponin - hypertrophic cardiomyopathy - lysosomal storage disorders - myocardial infarction

• Literatur

• 1 Desnick RJ. Brady R. Barranger J. et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003; 138: 338-346
• 2 Oder D. Uceyler N. Liu D. et al. Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y. Br Med J open 2016; 6: e010422
• 3 Lin HY. Chong KW. Hsu JH. et al. High incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population. Circulation. Cardiovascular genetics 2009; 2: 450-456
• 4 von Scheidt W. Eng CM. Fitzmaurice TF. et al. An atypical variant of Fabry's disease with manifestations confined to the myocardium. New Engl J Med 1991; 324: 395-399
• 5 MacDermot KD. Holmes A. Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Gen 2001; 38: 769-775
• 6 MacDermot KD. Holmes A. Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Gen 2001; 38: 750-760
• 7 Weidemann F. Niemann M. Breunig F. et al. Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation 2009; 119: 524-529
• 8 Germain DP. Charrow J. Desnick RJ. et al. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Gen 2015; 52: 353-358
• 9 Mehta A. Clarke JT. Giugliani R. et al. Natural course of Fabry disease: changing pattern of causes of death in FOS – Fabry Outcome Survey. J Med Gen 2009; 46: 548-552
• 10 Weidemann F. Maier SK. Stork S. et al. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy. Am J Cardiol Epub 2016 May 5 DOI: 10.1016/j.amjcard.2016.04.033.
• 11 Aerts JM. Groener JE. Kuiper S. et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Nat Acad Sci USA 2008; 105: 2812-2817
• 12 Togawa T. Kodama T. Suzuki T. et al. Plasma globotriaosylsphingosine as a biomarker of Fabry disease. Mol Gen Met 2010; 100: 257-261
• 13 Seydelmann N. Liu D. Kramer J. et al. High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease. J Am Heart Assoc 2016; 5 DOI: 10.1161/JAHA.115.002839.
• 14 Oder D. Liu D. Hu K. et al. P. V929 – Hereditäre Kardiomyopathien: Der Alpha-Galaktosidase A-Genotyp N215S als Differenzialdiagnose bei linksventrikulärer Hypertrophie unklarer Genese. Clin Res Cardiol 2016; 105 DOI: 10.1007/s00392-016-0967-z.
• 15 Sachdev B. Takenaka T. Teraguchi H. et al. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation 2002; 105: 1407-1411
• 16 Spada M. Pagliardini S. Yasuda M. et al. High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Gen 2006; 79: 31-40
• 17 Hwu WL. Chien YH. Lee NC. et al. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A). Human mutation 2009; 30: 1397-1405
• 18 Gensler D. Mörchel P. Fidler F. et al. Myocardial T1 Quantification Using an ECG-Triggered Radial Single-Shot Inversion Recovery Sequence. Radiology 2015; 274: 879-887
• 19 Rolfs A. Bottcher T. Zschiesche M. et al. Prevalence of fabry disease in patients with cryptogenic stroke: A prospective study. Lancet 2005; 366: 1794-1796
• 20 Uceyler N. Ganendiran S. Kramer D. et al. Characterization of pain in fabry disease. The Clinical journal of pain 2014; 30: 915-920
• 21 Germain DP. Hughes DA. Nicholls K. et al. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med 2016; 375 (06) 545-555