635 AMYLOIDOSIS AND THE ILE68LEU MUTATION OF THE TTR GENE: A RARE DISEASE YOU CAN TREAT.
Authors: Novembre Maria Laura 
Published: December 2022

Case presentation

During the last year, a 66-year-old man was repetitively hospitalized for anasarcatic heart failure in an infiltrative heart disease with an impaired left ventricular function.

In March 2022 the patient first presented to our emergency department with clinical signs of decompensated heart failure. An accurate diagnosis was made during the inpatient care.

The electrocardiogram documented sinus bradycardia, degree I atrioventricular block, and right bundle branch block. Echocardiography showed a slight reduction in biventricular function, concentric hypertrophy and a significant reduction in longitudinal systolic function (GLS -11.8%) with an apical-sparing pattern. At the same time, the presence of mild to moderate circumferential pericardial effusion was documented. According to the clinical suspicion, a cardiac MRI was performed, revealing consistent amyloid infiltrative disease. A 99-mTc-HDP myocardial scintigraphy confirmed pathological accumulation of trans-thyretine with a Perugini Score 2. Serum and urinary immunofixation were negative. A genetic test was subsequently performed whereby a heterozygous Ile68Leu (p.Ile88Leu) pathogenic mutation in the TTR gene was documented. Follow-up neurologic evaluation ruled out the indication to start Patisiran therapy due to the absence of significant neurologic involvement. In the meantime, the patient was put on Torasemide therapy with moderate clinical benefit. Few months ago, shortly after the diagnosis, the patient was hospitalized again for anasarcatic heart failure complicated by a severe ascites, underwent a paracentesis. During this hospitalization, therapy with Tafamidis was started. The patient is currently in good cardiovascular clinical compensation.

Discussion

This clinical case offers the chance to investigate the characteristics and phenotype of cardiac amyloidosis caused by the Ile68Leu mutation.

The typical Ile68Leu ATTRm patient is caucasian, tipically a 70 years’man (slightly younger than ATTRwt fenotipe), seeks medical attention with heart failure symptoms, and receives the correct diagnosis of cardiac amyloidosis almost 1 year after the onset of these symptoms.

Usually, the mutation leads to predominantly cardiac manifestations, instead of a combined form (cardiac and/or neurological manifestations). The Ile68Leu TTR mutation is a cause of cardiac amyloidosis that leads to a phenotype similar to ATTRwt.

The electrocardiogram and echocardiogram features described in the clinical case are typical and often indistinguishable from that of ATTRwt. The age at diagnosis and advanced heart failure symptoms at presentation were the only factors independently associated with mortality.

The subject patient is younger than the average affected ones and suffers from an aggressive form of the disease. The take home message could be that we should definitely learn and remember the importance of etiologic screening in infiltrative diseases, especially in young people, now that there are effective therapies capable to reduce mortality and improve quality of life.