P643 A case of Fabry cardiomyopathy refractory to enzyme replacement therapy; the importance of early diagnosis and treatment in Fabry cardiomyopathy

Abstract

A 56-year-old male was referred in order to identify Fabry disease after his older brother was confirmed as Fabry disease of cardiac variant type. He had been treated with hypertrophic cardiomyopathy (HCMP) five years ago. He didn’t have a history of hypertension. Blood pressure was 118/65 mmHg and pulse rate was 75 beats per minute. Serum creatinine was 1.07 mg/dl and estimated glomerular filtration rate was 75.2 ml/min. Cardiac enzymes including CK-MB and troponin-T were normal. There was no proteinuria on urinalysis. A 12-leads electrocardiogram revealed normal sinus rhythm with severe left ventricular hypertrophy (LVH) and strain pattern. Transthoracic echocardiogram (TTE) showed diffuse severe concentric hypertrophy of the left ventricle (LV) of an average ventricular wall thickness of 17 mm with normal systolic function (left ventricular ejection fraction (LVEF), 56%). TTE also revealed left ventricular outflow tract obstruction with systolic anterior motion of mitral valve. Right ventricle (RV) was also hypertrophied (RV free wall thickness, 7mm). Also, echocardiography revealed findings of diastolic dysfunction; left atrial enlargement, mitral inflow of a pseudo-normal pattern on pulsed wave Doppler image and an increased left ventricular filling pressure on tissue Doppler image (E/e’=20). Cardiac magnetic resonance imaging (MRI) revealed diffuse LV and RV hypertrophy and preserved LV systolic function with hypokinesia of mid-septal LV wall. Delayed hyper-enhancement (DHE) was not found within entire myocardium. A coronary CT angiography was performed because of regional wall motion abnormality but did not show any significant stenoses. He was confirmed as Fabry disease with the same genetic mutation as his brother. He did not present symptoms and signs of any other organs besides only myocardial hypertrophy. He received enzyme replacement therapy (ERT) with intravenous agalsidase-beta every other week via outpatient department for 3 years. Recently, TTE was performed and showed diffuse severe concentric LVH of an average ventricular wall thickness increased to 19 mm despite regularly ERT. Focal intramural and subepicardial DHE was newly developed at LV basal lateral and septal wall on cardiac MRI. Neutralizing antibody against agalsidase -beta was not found in serum.Fabry disease of cardiac variant type can be delayed in diagnostic aspect because of absence of typical symptoms and signs. Despite the absence of neutralizing antibody, ERT did not prevent both further myocardial hypertrophy and myocardial fibrosis in patient with advanced myocardial hypertrophy caused by delayed diagnosis of Fabry disease. Suspicion of Fabry disease through detailed history taking including family history in patients with diffuse ventricular hypertrophy on an echocardiography can lead to early diagnosis and treatment and can result in improvement in a clinical outcome.