Wild-type (senile) ATTR amyloidosis history and symptoms

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

History

• Coexistence of both cardiac and peripheral nervous system (PNS) involvement should always raise suspicion for ATTR-related amyloidosis.

Symptoms

The clinical manifestations of TTR-related amyloidosis (ATTR) are determined by

• The subtype of transthyretin (TTR) protein mutation
• Tissue distributio
• The amount of amyloid deposition.

Common symptoms of ATTR include:

Symptoms
Cardiovascular involvement	Symptoms of chronic heart failure Severe postural hypotension (due to deposition in the subendothelium of the peripheral vasculature)
Neuropathic involvement	Peripheral nerve problems are the presenting complaints in most cases of ATTR Most often symmetric 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 Patients with peripheral nerve deposits note sensorimotor impairment. While the majority present with bilateral, lower-to-upper extremity symptoms, as described above, some TTR variants present as lower-limb neuropathy (eg, TTR V30M), while other variants present as primarily upper-limb neuropathy (eg, TTR I84S, TTR L58H). 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.
Other manifestations	Patients with gastrointestinal deposits present with alternating diarrhea and constipation. Nausea and vomiting also occur. Weakness and paresthesias of one or both hands, suggesting carpal ligament involvement, is often the presenting symptom in patients with the variant TTR L58H. Ophthalmological involvement may present as follows: Dry eye, red eye, painful eye, conjunctivitis Floaters in eyes, decreased visual acuity