When should a cardiologist suspect Fabry disease?
The information on this page is tailored for cardiologists. For more detailed information on the cause, inheritance, diagnosis and management of Fabry disease, please refer to our ‘About Fabry disease’ page.
Cardiac signs in fabry disease
As Fabry disease progresses, cardiac symptoms and cardiomyopathy develop, as indicated by myocardial fibrosis, which, in end-stage patients, can result in congestive heart failure and death.1 It is for this reason that early diagnosis of Fabry disease is paramount.
As such, along with cardiac impairment, patients exhibiting the following signs should be considered.
Systematically consider Fabry disease in males ≥ 30 years and females ≥ 40 years particularly if:
- Extracardiac abnormalities: kidney dysfunction, stroke/TIA (Transient Ischaemic Attack), angiokeratoma, cornea verticillata
- ECG (Electrocardiogram)/48–hour Holter: short PR interval, AV (Atrioventricular) block, decreased HRV (Heart Rate Variability), pacemaker, arrhythmias
- Echocardiography: concentric LVH (13–22 mm), non–obstructive HCM (Hypertrophic cardiomyopathy), abnormal infero–lateral longitudinal strain, right ventricular hypertrophy, thinning of the basal infero–lateral LV wall
- Cardiac MRI: postero-lateral LGE (Late Gadolinium Enhancement), reduction in non–contrast T1 signal, elevated T2
- Biological testing: decreased GFR (Glomerular Filtration Rate), proteinuria, high–sensitivity troponin (hs–TNN)
- Family history: no father–to–son transmission, cryptogenic stroke, severe kidney failure
Refer patients for genetic testing at Fabry disease/HCM reference centres:
- Males: α-Gal A and gene testing
- Females: gene testing
This table outlines the prevalence of Fabry disease reported from studies in patients with hypertrophic cardiomyopathy (HCM).
|Saito et al., 20153||508 patients with HCM||1% (0.9% in men, 1.1% in women)|
|Sachdev et al., 20024||153 male patients with HCM||3.9% of males|
|Palecek et al., 20145||100 male patients with unexplained LVH||4% of males|
|Chimenti et al., 20046||34 female patients with late-onset HCM||12% of females|
Damage to both the heart and the kidneys in Fabry disease may lead to ‘cross-talk’ and development of secondary cardiorenal syndrome, often with insidious onset. However, this is a very late sign of Fabry disease.7
Identifying symptoms beyond cardiac impairment is critical to establishing a diagnosis. Non-cardiac manifestations may include:1
Proteinuria and progressive renal failure
Acroparaesthesia, pain crises, neuropathic pain; pain is a common early symptom of Fabry disease, often beginning in adolescence
Abdominal pain (often after eating), nausea, vomiting
Cornea verticillata, retinal tortuosity
Angiokeratoma and dyshidrosis
Ultimately, referral to nominated ultra-specialist centres is required so that patients can access full genetic testing and access to disease-specific therapies.
This figure displays the centres that specialise in the testing and management of Fabry disease.
Tap on each pin on the map to learn more.
- Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.
- Hagège A, Réant P, Habib G, et al. Fabry disease in cardiology practice: literature review and expert point of view. Archives Cardio Dis. 2019;112:278–287.
- Monserrat L, Gimeno-Blanes JR, Marin F, et al. Prevalence of Fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy. J Am College Cardio. 2007;50:2399–2403.
- 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.
- Palecek T, Honzikova J, Poupetova H, et al. Prevalence of Fabry disease in male patients with unexplained left ventricular hypertrophy in primary cardiology practice: prospective Fabry cardiomyopathy screening study (FACSS). J Inherit Metab Dis. 2014;37:455–460.
- Chimenti C, Pieroni M, Morgante E, et al. Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation. 2004;110:1047–1053.
- Sharma A, Sartori M, Zaragoza JJ, et al. Fabry’s disease: an example of cardiorenal syndrome type 5. Heart Fail Rev. 2015;20:689-708.
Cardiac pathophysiology in Fabry disease
Management of Fabry disease