Hereditary transthyretin amyloidosis caused by a rare mutation

Transthyretin amyloidosis (ATTR) is an underdiagnosed multisystem disease. More than 140 known mutations are pathologic, and organ tropism can vary significantly based on the causative mutation. An elderly man with neuropathy and congestive heart failure was found to have left ventricular hypertrophy on echocardiogram. Subsequent endomyocardial biopsy demonstrated transthyretin amyloid deposition. On referral to our centre, genetic testing was performed, demonstrating a missense mutation, c.229G>A, that results in the amino acid substitution p.Gly77Arg. This mutation had only been reported in one other case of amyloidosis internationally. Cascade genetic testing ensued, which resulted in multiple family members having the same mutation with varying stages of disease activity. This case highlights the importance of genetic testing for all individuals diagnosed with ATTR regardless of age and the variable organ tropism of the disease.