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transthyretin amyloidosis; ATTR amyloidosis

Etiology: - transthyretin cardiac amyloidosis - oculoleptomeningeal type amyloidosis (amyloidosis VII) Pathology: - progressive axonal polyneuropathy - sensory polyneuropathy - motor polyneuropathy - autonomic polyneuropathy Genetics: - family history of neuropathy, restrictive cardiomyopathy - mutation in transthyretin gene (TTR) Clinical manifestations: - multiorgan involvement common - peripheral neuropathy (sensory neuropathy) - carpal tunnel syndrome - paresthesia - ataxia - autonomic neuropathy: orthostasis, syncope, dry mouth - eyes: glaucoma, dry eyes - GI: constipation - GU: erectile dysfunction - heart failure: restrictive cardiomyopathy - Popeye sign (retraction of biceps brachii) [6] Laboratory: - transthyretin gene mutation Special laboratory: - electromyography with nerve conduction study - diffuse axonal sensorimotor polyneuropathy - periodic cardiac screening with speckle-tracking echocardiography & radionuclide cardiac scintigraphy [4] Radiology: - cardiac magnetic resonance imaging Management: - tafamidis 20-80 mg QD - reduces mortality, cardiovascular hospitalization [7] - TTR mRNA-guided CRISPR-Cas9 system with durable knockout of TTR in 6 patients with transthyretin amyloidosis after a single dose [5] - vutrisiran (Amvuttra) a transthyretin-directed small interfering RNA - 25 mg once every 3 months - symptomatic treatment with loop diuretics, mineralocorticoid receptor antagonists, SGLT-2 inhibitors [7]

Related

transthyretin; ATTR; prealbumin; TBPA (TTR PALB)

Specific

transthyretin cardiac amyloidosis; amyloid transthyretin cardiomyopathy (ATTR-CM)

General

senile systemic amyloidosis familial amyloidosis

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 18, 19. American College of Physicians, Philadelphia 2018, 2022.
  2. Adams D, Lozeron P, Lacroix C. Amyloid neuropathies. Curr Opin Neurol. 2012 Oct;25(5):564-72. Review. PMID: 22941262 - Adams D, Cauquil C, Labeyrie C. Familial amyloid polyneuropathy. Curr Opin Neurol. 2017 Oct;30(5):481-489. Review. PMID: 28678039
  3. ARUP Consult: Familial Transthyretin Amyloidosis (TTR) Sequencing https://arupconsult.com/ati/familial-transthyretin-amyloidosis-ttr-sequencing
  4. Sinha A, McNally EM, Khan SS Transthyretin Genetic Testing. JAMA Cardiol. Published online May 12, 2021 PMID: 33978672 https://jamanetwork.com/journals/jamacardiology/fullarticle/2779773
  5. George J In a First, CRISPR Infusion Edits Genes Directly in Humans. "A watershed moment in modern medicine," says genetics expert. MedPage Today June 28, 2021 https://www.medpagetoday.com/neurology/generalneurology/93314 - Gillmore JD, Gane E, Taubel J et al CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med 2021. June 26 PMID: 34215024 https://www.nejm.org/doi/full/10.1056/NEJMoa2107454
  6. Nomura T, Fujiki F, Ueda M. Popeye Sign in Hereditary Transthyretin Amyloidosis. JAMA Neurol. Published online July 3, 2023 PMID: 37399023 https://jamanetwork.com/journals/jamaneurology/fullarticle/2806405
  7. Di Palo, Feder S, Baggenstos YT et al Palliative Pharmacotherapy for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circ Cardiovasc Qual Outcomes. 2024 Jul 1:e000131 PMID: 38946532 Free article. Review. https://www.ahajournals.org/doi/epdf/10.1161/HCQ.0000000000000131