Transthyretin-Related Amyloidosis Treatment & Management

  • Author: Jefferson R Roberts, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Aug 15, 2011
 

Medical Care

No pharmacologic therapy is available that reverses the process of TTR amyloid formation. Thus, care generally is limited to supportive measures.

Cardiac involvement

Diuretics are the mainstay of therapy for amyloid-related congestive heart failure (whether ATTR, AL, or, rarely, another type). The optimal degree of diuresis often is difficult to judge. When edema is troubling and symptomatic postural hypotension is not present, fluid can be removed with careful diuresis. On the other hand, hypotension resulting from a low ejection fraction and/or autonomic neuropathy may limit diuretic use.

Digoxin and calcium channel blockers are contraindicated in cardiac amyloidosis. Digoxin is ineffective and is associated with morbidity and mortality. Calcium channel blocking agents bind to amyloid fibrils, presumably leading to local toxic concentrations, and can worsen congestive heart failure in patients with cardiac amyloidosis.

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Surgical Care

  • Liver transplantation
    • An important therapeutic advance for this condition is liver transplantation, first performed for FAP in 1990. More than 1700 liver transplants have been reported to the Familial Amyloid Polyneuropathy World Transplant Registry (FAPWTR). In suitable patients, this replaces the source of variant TTR with a source of normal-sequence TTR, sometimes leading to gradual fibril resorption and disease stabilization, especially of neurologic complications. Liver transplantation seems to halt progression of sensory, motor, and autonomic neuropathy.[17] Ideally, the transplantation should be performed as early in the disease course as possible, before significant neurologic disability has been incurred.[18]
    • However, patients with cardiac, leptomeningeal, gastrointestinal, or ocular involvement often progress despite transplantation.
    • The identification of TTR variants in patients who clinically could have either SCA or unrecognized familial ATTR is important because liver transplantation would not benefit patients with deposition of normal-sequence TTR. On the other hand, patients with normal-sequence ATTR could be included in experimental trials of drugs that might inhibit or reverse deposition.[19]
    • Initial studies involving small cohorts of patients showed short-term survival rates of 77%-88%. The registry has recently collected data from several centers reporting an overall 5-year survival rate of 75%.[20]
  • Combination heart and liver or liver and kidney transplantation has been performed in select patients, with variable success, and an 18.1% rate of postoperative cardiac complications has been shown with heart transplantations.[21]
  • Carpal tunnel release
    • Involvement of the carpal ligament is observed not only in ATTR but also, most commonly, in Ab2 M in patients undergoing dialysis and in patients with AL (see Amyloidosis, Beta2M [Dialysis Related] and Amyloidosis, Immunoglobulin-Related). Treatment is surgical.
    • At the time of carpal tunnel release, a biopsy should be performed if a definitive diagnosis has not been established previously so that both Congo red staining and immunostaining can be performed. Why the carpal ligament, or indeed any organ, is a favored location for amyloid deposition is not known.
  • Vitrectomy: Vitrectomy is useful in patients with vitreous involvement.
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Diet

Diet is not known to affect ATTR. However, patients with congestive heart failure due to ATTR should receive appropriate dietary management for that condition.

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Contributor Information and Disclosures
Author

Jefferson R Roberts, MD  Staff Physician, Department of Rheumatology, Walter Reed Army Medical Center; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine

Jefferson R Roberts, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Robert John Oglesby, MD  Chief of Rheumatology Service, Department of Medicine, Walter Reed Army Medical Center; Associate Professor of Medicine, Uniformed Services University of the Health Sciences

Robert John Oglesby, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and Arthritis Foundation

Disclosure: Nothing to disclose.

Aaron Pumerantz, DO  Fellow Instructor, Department of Medicine, Uniformed Services University of the Health Sciences

Aaron Pumerantz, DO is a member of the following medical societies: American College of Physicians, American Medical Association, and American Osteopathic Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert E Wolf, MD, PhD  Professor Emeritus, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Administration Medical Center of Shreveport

Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, and Society for Leukocyte Biology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Lawrence H Brent, MD  Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Genentech Honoraria Speaking and teaching; Genentech Grant/research funds Other; Amgen Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching; Takeda Honoraria Speaking and teaching; UCB Speaking and teaching; Omnicare Consulting fee Consulting; Centocor Consulting fee Consulting

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthors Seetha U Monrad, MD; Mariana J Kaplan, MD; and Daniel R Jacobson, MD, to the development and writing of this article.

References

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  21. Lauro A, Diago Usò T, Masetti M, Di Benedetto F, Cautero N, De Ruvo N, et al. Liver transplantation for familial amyloid polyneuropathy non-VAL30MET variants: are cardiac complications influenced by prophylactic pacing and immunosuppressive weaning?. Transplant Proc. Jun 2005;37(5):2214-20. [Medline].

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Congo Red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light.
Table 1
VariantGeographic Focus (Ethnic Origin)Organs Involved
Gly6SerCaucasianNone
Cys10ArgUnited States (Hungarian)H, PN, AN, E
Leu12ProUnited KingdomCNS, AN, L, LM
Asp18GlyUnited States (Hungarian)CNS, LM
Met13IleGermanyNone
Asp18AsnUnited StatesH
Asp18GluSouth AmericaAN, PN
Val20IleUnited States, GermanyH, CL
Ser23AsnUnited States (Portuguese)H, E, PN
Pro24SerUnited StatesPN, H, CL
Ala25SerUnited StatesH, PN
Ala25ThrJapanCNS, PN
Val28MetPortugalAN, PN
Val30MetArgentina, Brazil, China, Finland, France, Germany, Greece, Italy, Japan, Portugal, Sweden, Turkey, United StatesPN, AN, E, LM
Val30AlaUnited States (German)AN, H
Val30LeuJapan, United StatesPN, AN, H, K
Val30GlyUnited StatesE, CNS, LM
Phe33CysUnited StatesCL, E, K, H
Phe33IleIsrael (Polish, Ashkenazi Jewish)PN, E
Phe33LeuUnited States (Polish, Lithuanian)PN, AN
Arg34ThrItalyPN, H
Lys35AsnFrancePN, H, AN
Ala36ProGreece, Italy, United States (Jewish)PN, E, CNS, CL
Asp38AlaJapanH, PN, AN
Trp41LeuUnited States (Russian)E
Glu42GlyJapan, Russia, United StatesPN, AN
Glu42AspFranceH
Phe44SerUnited States, JapanPN, H, AN, E
Ala45ThrItaly, Ireland, United StatesH
Ala45AspUnited States , Ireland, ItalyPN, H
Ala45SerSwedenH
Gly47AlaItaly, Germany, FrancePN, H, AN
Gly47ArgJapanPN, AN
Gly47ValSri LankaH, AN, PN, CL
Gly47GluGermany, ItalyH, K, PN
Thr49AlaFrance, Italy (Sicily)PN, CL, H
Thr49IleJapanPN, H
Thr49ProUnited StatesH
Ser50ArgJapan, France, ItalyPN, H, AN
Ser50IleJapanPN, H, AN
Glu51GlyUnited StatesH
Ser52ProUnited KingdomPN, AN, H, K
Gly53GluBasqueCNS, LM, PN
Glu54GlyUnited KingdomPN, E, AN
Glu54LysJapanPN, AN, H
Leu55ProUnited States (Dutch, German), TaiwanPN, E, H, AN
Leu55ArgGermanyPN, LM
Leu55GlnUnited States (Spanish)AN, E, PN
Leu58HisUnited States, GermanyH, CL
His56ArgUnited StatesH
Leu58ArgJapanAN, E, CL, H
Thr59LysItaly, United States (Chinese)H, PN, AN
Thr60AlaIreland, United States, Australia, Germany, United Kingdom, JapanH, PN, GI, CL
Glu61LysJapanPN
Phe64LeuItaly, United StatesPN, H, CL
Phe64SerCanada (Italian), United KingdomCNS, PN, E, LM
Ile68LeuGermany, United StatesH
Tyr69HisUnited States, ScotlandE
Tyr69IleJapanCL, H
Lys70AsnUnited States, GermanyCL, E, PN
Val71AlaFrance, SpainPN, E , CL
Ile73ValBangladeshPN, AN
Asp74HisGermanyNone
Ser77TyrGermany, France, United KingdomPN, H, K
Ser77PheFrancePN, AN
Tyr78PheFrance (Italian)PN, CL, S
Ala81ThrUnited StatesH
Ile84SerUnited States (Swiss), HungaryH, CL, E, LM
Ile84AsnItaly, United StatesE, H, CL
Ile84ThrGermany, United KingdomPN, AN, H
Glu89GlnSicilyPN, H, CL
Glu89LysUnited StatesPN, H, AN
His90AsnPortugal, GermanyNone
Ala91SerFrancePN, H, CL, AN
Arg104CysUnited StatesNone
Arg103SerUnited StatesH
Pro102ArgGermanyNone
Ala97SerChina, France, TaiwanH,PN
Gln92LysJapanH
Ala97GlyJapanPN,H
Gly101SerJapanNone
Arg104HisJapan, United States (Chinese)None
Ile107MetGermanyH, PN
Ile107ValUnited States(German), JapanPN, H, CL
Ala109ValUnited StatesNone
Ala108AlaPortugalNone
Ala109ThrPortugalNone
Ala109SerJapanPN
Leu111MetDenmarkH, CL
Tyr114CysHollandPN, E, H, LM, AN, CNS
Tyr114HisJapanCL
Tyr116SerFrancePN, CL, AN
Thr119MetUnited States, PortugalNone
Ala120SerAfro-CaribbeanPN, H, AN
Val122IleAfrica, United States, PortugalH
Val122AlaUnited States (Alaska), United KingdomPN, H, E
Deletion of 122ValEcuador, United StatesPN, CNS, GI, CL, H
Pro125SerItalyNone
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