Prevalence of Anderson-Fabry disease in a cohort with unexplained late gadolinium enhancement on cardiac MRI

Abstract

Introduction

Fabry disease is a rare X-linked genetic disorder in which cardiac manifestations include LVH, contractile dysfunction, and fibrosis, visible on cardiac MRI (cMRI) as late gadolinium enhancement (LGE) of the myocardium. Fabry's disease is an important diagnosis to make as treatment is available as lifelong replacement of the deficient enzyme.

Aim

To define the prevalence of Fabry disease in a cohort of patients with unexplained LGE on cMRI.

Methods

The study population was recruited from patients aged >16 years who had cMRI performed between 2010 and 2018 to investigate LVH, idiopathic LV dysfunction and/or idiopathic ventricular arrhythmia. Patients with ‘unexplained’ LGE i.e. without a genetic diagnosis of an alternate cardiomyopathy such as HCM or biopsy-proven infiltrative cardiomyopathy such as sarcoid or amyloid, were tested for Fabry disease by either genetic testing or the Dried Blood Spot test (Sanofi-Genzyme).

Results

Of the 79 patients with unexplained LGE on cMRI, 2 patients tested positive for Fabry disease, both using genetic sequencing techniques. The prevalence of Fabry disease in this selected cohort was 2.5%. Specifically, 1 patient was a 65 year old male and the other patient a 75 year old female. In both cases, the pattern and distribution of LGE on cMRI was of patchy mid-wall enhancement in the inferoseptum.

Conclusion

Unexplained LGE on cMRI may be an isolated manifestation of late-onset Fabry disease. This finding should prompt testing for Fabry disease given this is a potentially treatable condition.

Introduction

Anderson-Fabry's disease (AFD) is a rare X-linked lysosomal storage disorder in which cardiac involvement includes left ventricular hypertrophy (LVH) or dilated cardiomyopathy (DCM), contractile dysfunction, and chronic myocardial inflammation / fibrosis, visible on cardiac MRI (cMRI) as myocardial late gadolinium enhancement (LGE) in up to 50% of affected patients [1].

The diagnosis is made by demonstrating deficient plasma ɑ-galactosidase A (ɑ-Gal A) enzyme activity in males; or detecting pathogenic variants in the GLA gene using molecular genetic testing methods in males and females [2]. AFD is an important diagnosis to make early as treatment is available as lifelong replacement of the deficient alpha-galactosidase enzyme, however the low prevalence of this rare disease means that population screening is not a cost-effective diagnostic strategy. Targeted testing of patients with possible AFD-related cardiac involvement significantly improves detection rates (AFD screening in HCM); and cardiac MRI is the diagnostic test of choice for detecting LVH and cardiac infiltration and chronic inflammation, seen as myocardial LGE. The aim of this study was to define the prevalence of Fabry disease in a cohort of patients with unexplained LGE on cMRI, and to evaluate the utility of including AFD testing in the diagnostic algorithm for unexplained LGE.