Fabry Disease in High-risk Patients With Left Ventricular Hypertrophy: Prevalence and Implementation of a Clinical Score

Aims of the study:

To evaluate the prevalence of Fabry Disease (FD) among a cohort of high risk patients with left ventricular hypertrophy (LVH) presenting at the University Hospital Würzburg over the last 10 years. Fabry disease is a rare disease that is known to be consistently underdiagnosed due to its largely variable symptoms. Considering that an early Fabry diagnosis is crucial for maximum benefit from therapies available, screening for Fabry patients can contribute to preventing development and worsening of symptoms in Fabry patients with LVH. In addition, a positive diagnosis in a family member opens the possibility to diagnose further family members in an earlier stage of the disease, therefore allowing treatment of symptoms and organ manifestations before they become irreversible.

Background:

Fabry disease (FD) is a rare X-linked disease caused by enzyme α-Galactosidase A (αGAL) deficiency resulting from mutations in the gene encoding this enzyme. Many patients present with a "private" specific mutation found only in that particular family and, thus, several hundreds of mutations are currently known. This multiplicity in mutations contributes to large variations in residual enzyme activity and different clinical presentations (Baptista A, 2015). Due to this variable phenotype, the disease is still largely underdiagnosed. Therefore, the reports of a prevalence of ~1 per 40,000 / 100,000 persons in the general population are probably an underestimation (Terryn W, 2013). Previous screening studies for FD in high risk populations (left ventricular hypertrophy) report much higher frequencies, highlighting the need of including this disease among the differential diagnoses of left ventricular hypertrophy (LVH) of unexplained origin (Terryn W, 2012; Baptista A, 2015).

Left ventricular hypertrophy (LVH), detected both by imaging techniques (echocardiography, MRI) and by electrocardiography (ECG) is the predominant cardiac finding in Fabry patients (Linhart A, 2006). In a cross sectional study of untreated FD patients, half of the men and one third of the women were classified as having LVH (defined as LVMi of >51 g/m2.7 for males and >48 g/m2.7 for females) (Kampmann C, 2008). In screening studies in patients with LVH, the prevalence of FD is higher, including reports of a prevalence of up to 12% (Terryn W, 2012). Considering that enzyme replacement therapy (ERT) has been shown to significantly reduce left ventricular mass and wall thickness, an early diagnosis and treatment of these patients has the potential to modify the natural course of the disease and reduce morbidity and mortality. In addition, it offers the important possibility to diagnose family members in an earlier stage of the disease.