Early-Onset Vitreous and Cardiac Amyloidosis With TTR Trp61Leu.

Abstract

The pathogenic transthyretin (TTR) gene variant c.182G>T, p.Trp61Leu (Trp61Leu) was previously reported once, as variant transthyretin amyloidosis (ATTRv) manifesting with vitreous and cutaneous involvement, with symptom onset at age 42. We report updated clinical progression of Trp61Leu-associated ATTRv in an patient (the proband) and her 2 daughters, who represent the first known cases of Trp61Leu cardiac amyloidosis (CA) with onset before age 40. This early-onset CA stands in stark contrast to that observed with most other ATTRv genotypes and is further highlighted by the finding that technetium pyrophosphate scans were severely abnormal before any echocardiographic abnormalities became apparent. We also report an unrelated patient with wild-type germline TTR who developed ATTR after receiving the proband's transplanted liver through a domino procedure. Furthermore, vitreous amyloid preceded CA in 3 of 4 cases, highlighting an important and often overlooked "red flag" feature of ATTRv not addressed with existing transthyretin silencer or stabilizing therapies.