History
The subtype of TTR protein mutation, its tissue distribution, and the amount of amyloid deposition largely determine the clinical manifestations of ATTR. The key characteristic of ATTR that should raise clinical suspicion for this disorder remains the reliable coexistence of both cardiac and peripheral nervous system (PNS) involvement. This association will require the clinician to adequately interview the patient, who is likely to be presenting with a chief complaint related to one but not both organ systems. Patient presentation, including history and symptoms, can help to identify organ system involvement. Specific organ system involvement will determine the complications the patient will face.
Cardiovascular involvement
Patients with cardiac deposition often present with signs and symptoms suggesting chronic heart failure (ie, dyspnea on exertion, peripheral edema) and/or arrhythmias (ie, palpitations, lightheadedness, syncope). [16]
Neuropathic involvement
Peripheral nerve problems are the presenting complaints in most cases of ATTR and can be reliably differentiated from other types of PNS disease by the fact that they are most often symmetrical, distal polyneuropathies that typically begin in the lower limbs, progress to the upper limbs, and then affect more proximal aspects of the limbs and the trunk. A family history of a similar polyneuropathy is usually present and hence warrants a rigorous family history discussion as part of the history.
Patients with peripheral nerve deposits note sensorimotor impairment. While the majority present with bilateral, lower-to-upper extremity symptoms, some TTR variants present as lower-limb neuropathy (eg, TTR V30M), and other variants present as primarily upper-limb neuropathy (eg, TTR I84S, TTR L58H). [1]
Neuropathy in patients with ATTR V30M often presents as lower extremity weakness, pain, and/or impaired sensation. Autonomic dysfunction, often manifested as sexual or urinary dysfunction, is common. [20]
Other manifestations
Patients with gastrointestinal deposits present with alternating diarrhea and constipation. Nausea and vomiting also occur.
Weakness and paresthesia of one or both hands, suggesting carpal ligament involvement, are often the presenting symptoms in patients with the variant TTR L58H. It can also be observed in patients with other variants, including wild-type (normal-sequence) TTR. Carpal tunnel syndrome may precede other clinical manifestations, sometimes by as much as 20 years.
Ophthalmologic involvement may present as follows:
- Dry eye, red eye, painful eye, conjunctivitis
- Floaters in eyes, decreased visual acuity