Experts Publish ATTRv Amyloidosis Recommendations for US Clinicians

Citing a lack of guidance in the United States addressing hereditary transthyretin (ATTRv; v for variant) amyloidosis with polyneuropathy, a group of 7 neurologists with expertise in ATTRv amyloidosis published recommendations for identifying, monitoring, and treating patients with the disease in the journal Muscle & Nerve.

“Part of the challenge in the United States is that many genetic variants are present and there is no characteristic disease presentation, unlike endemic regions (eg, Portugal, Brazil, and Japan),” wrote corresponding author Chafic Karam, MD, of the University of Pennsylvania, Philadelphia, Pennsylvania, and coauthors. “Hence, a US-relevant guideline is needed.”

According to the guidance, clinicians should consider possible ATTRv amyloidosis with polyneuropathy in patients with unexplained progressive neuropathy associated with family history or systemic symptoms. Presenting symptoms vary and can include:

• sensory symptoms, such as pain, altered sensation, tingling/prickling sensations, and imbalance;
• motor symptoms, such as distal muscle weakness and atrophy, tripping, foot drop, walking difficulties, difficulty opening jars, dexterity loss, and difficulty climbing stairs/rising from a chair; and
• autonomic symptoms, such as erectile dysfunction, genitourinary problems, gastrointestinal manifestations, lightheadedness/orthostatic hypotension/syncope/presyncope, loss of hair/sweating abnormalities, heat intolerance, blurred vision/dry eyes, and dry mouth.

“The diagnosis is confirmed through genetic testing, biopsy, or cardiac technetium-based scintigraphy,” researchers advised.

Because the disease is progressive and associated with poor prognosis, early identification and timely therapeutic intervention are important. The authors recommend gene-silencing therapeutics as a first-line treatment because evidence shows their benefit in both patients with early-stage and patients with more advanced ATTRv amyloidosis with polyneuropathy.

Evidence is currently lacking about what constitutes “disease progression” during treatment, as well as how to treat patients who do not respond or worsen on treatment, how to manage central nervous system or ocular manifestations, and how to care for asymptomatic patients, the authors advised.

“Ongoing or planned clinical trials in patients with ATTRv amyloidosis with polyneuropathy remain fundamental,” researchers wrote, “to provide robust evidence to support future recommendations in this rapidly evolving field.”

Reference

Karam C, Mauermann ML, Gonzalez-Duarte A, et al. Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: recommendations from a panel of experts. Muscle Nerve. 2024;69(3):273-287. doi:10.1002/mus.28026