Variable Presentation of Hereditary Transthyretin-Mediated Amyloidosis at a Single Center

Describe atypical presentations of hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy.

Initial symptoms, diagnoses, and follow-up were recorded at the Austin Neuromuscular Center for 12 patients with nonclassical presentation of hATTR amyloidosis.

Common initial symptoms were hand and/or feet sensory manifestations (83%), muscle weakness (58%), and, less frequently, gastrointestinal and orthostatic impairment and carpal tunnel syndrome. Initial diagnoses were polyneuropathy (83%) and/or myopathy (25%). During follow-up, 10 patients (83%) developed cardiac symptoms (dyspnea, 67% and ankle edema, 17%), resulting in revised diagnoses of heart disease. Multisystem involvement raised suspicion of amyloidosis, which was confirmed by biopsy or nuclear scintigraphy, and genetic testing. All patients had polyneuropathy; 8 (67%) had cardiomyopathy-associated transthyretin mutations (V122I or T60A). Time from symptom onset to diagnosis was up to 10 years (median 5 years), during which patients' health deteriorated, although with recognition of disease signs/symptoms the diagnosis of hATTR amyloidosis was made in approximately 2-6 months from presentation at our center.

Increased awareness of the diverse initial hATTR amyloidosis symptoms could shorten time to diagnosis, enabling earlier treatment and improved patient outcomes.