Cardiac amyloidosis: rare association of VAL142ILE and VAL50MET pathogenic variants

ABSTRACT

INTRODUCTION: Cardiac amyloidosis is a underdiagnosed cause of heart failure. Hereditary transthyretin amyloidosis can occur in more than 130pathogenic variants with variable clinical presentation depending on the type of mutation. They two main phenotypes are peripheral polyneuropathy and amyloidotic heart disease. The variant Val50t is the most prevalent in the world and most important representative of the polyneur phenotype. Val142Ile is the second most prevalent and is mostly expressed with heart disease. We describe a patient who presents a rare association of these two pathogenic variants in composed heterozygosity. Case report A 66-year-old black male patient from Juazeiro-BA, previously healthy, with a family history of neuropathy and heart disease in two brothers who died with 64 and 73 years old. She had altered sensitivity in the tips of her fingers, hands and feet, burning pain and reduced strength in her left leg and both hands for tree years. She also reported weight loss of 9 kg in two years, dizziness when assuming an orthostatic position and early satiety. Cardiological complaints were just heart palpitations during exercise and lower limb edema. In physical examination she presented with postural hypotension, rediced grip strength and pinching movement in the fingers and atrophy of the intrinsic muscles of the hands. Electrocardiogram left anterior fascicular block and inactive zone of inferior and anterior walls. Echocardiogram preserved left ventricle ejection fraction (global longitudinal strain of -8.7%), grade III diastolic dysfunction and enlargement of the left ventricle wall (20mm) and interatrial septum (9mm). Pyrophosphate scintigraphy showed pergini grade 3 uptake with a 2.22 rate. Genetic sequencing demonstrated the presence of two pathogenic variants on chromosome 18, both in heterozygosity Val50Met and VAL142Ile. CONCLUSION: an association of two pathogenic variants is rare and is associated with a more severe expression of the disease and worse prognosis. In this case the apresentation was mixed heart disease, polyneuropathy and dysautonomia, with a predominance of the last one. Heart disease symptoms were not exuberant, perhaps because of the physical limitation of the patient. However, the uptake of pyrophosphate on scintigraphy was much more intense than usual, suggesting high degree of deposit and worse prognosis.