Understanding hATTR Amyloidosis With Polyneuropathy

Table of ContentsView AllTable of ContentsSymptomsRisks and ComplicationsTreatmentPrognosis

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Table of Contents

Symptoms

Risks and Complications

Treatment

Prognosis

Hereditary transthyretinamyloidosiswithpolyneuropathy(damage to yourperipheral nerves), (hATTR-PN), is a rare disease that attacks your nervous system. It occurs when a defect in the transthyretin (TTR) protein is passed to you from a parent.

The damaged gene changes the shape and function of TTR. When normal, TTR transportsthyroid hormoneandvitamin Athrough your body.

Damaged TTR will likely cluster and form toxic amyloid deposits in your nerves, heart, and other tissue. This form of the disease mainly affects your sensory functions that involve touch, pressure, and pain.

Having hATTR-PN can make it hard to move and perform daily tasks. When found early, some cases may slow or improve from novel treatments that target how much damaged TTR your body makes.

This article explains the symptoms, risks, and complications of this disease. It also includes treatments, disease outcomes, and ways to cope.

Thai Liang Lim / Getty Images

person holding ankle

hATTR Amyloidosis and Polyneuropathy Symptoms

The condition hATTR amyloidosis with polyneuropathy, also known as familial amyloidosis with polyneuropathy, is considered the most serious hereditary polyneuropathy of adult-onset disease. The disease onset and presentation are typically progressive, devastating, and life-threatening.

Symptoms of this rare disease can be highly varied based on the specific mutation that develops. There are more than 120 mutations in the TTR gene. The predominant clinical feature will give hATTR its name as either polyneuropathy (hATTR-PN) or cardiomyopathy (hATTR-CM). One of the most common variations is hATTR amyloidosis with polyneuropathy. Most people have a combination of both heart and nerve involvement.

Advancing or late-stage (onset at age 50 or older) hATTR-PN tends to proceed with the following symptoms related to the peripheral nervous system:

Types of Amyloidosis Symptoms

Risks associated with having hATTR-PN are passed from parent to child in anautosomal dominant manner. You have a 50% chance of inheriting the TTR mutation if one of your parents is affected or known to have the variant. While the majority of people who have hereditary amyloidosis develop symptoms, some of those affected never get the disease.

The variability of disease onset and presentation differs based on factors including your country of origin and the parent’s gender from whom you inherited the mutation. The Val30Met mutation is the most common TTR mutation worldwide, accounting for about half of TTR variants globally. It is typically associated with polyneuropathy.

While hATTR-PN predominantly affects your nervous system, it is a systemic disease, meaning it affects other organs and tissue as well. When amyloid deposits interfere with normal function in other areas, the following complications can occur:

Treatment to Manage hATTR Amyloidosis With Polyneuropathy

As recently as 1990, the only treatments available for hATTR-PN were therapies to manage symptoms because the condition was regarded as incurable. However, novel therapies have improved disease outcomes since then.

Drug Treatments

While the specific therapy you receive depends on many factors, early diagnosis is critical to achieve the best results. Newer treatments are most effective during the early stages of the disease. They have successfully lowered TTR levels, reduced neuropathic symptoms, and improved quality of life. Some treatments may also help slow disease progression.

Treatment to manage hATTR-PN includes the following pharmacotherapies:

TTR gene silencers that interfere with the production of the TTR protein in your liver:

TTR stabilizers that prevent the TTR proteins from misfolding and forming amyloid deposits:

Amyloid fibrils degraders that degrade or destroy existing amyloid deposits:

Liver Transplant

Until the recent approval of pharmacotherapies for hATTR amyloidosis, liver transplantation was the only available treatment. It is most effective for people with early-onset hATTR amyloidosis with polyneuropathy.

However, liver transplantation is costly and of high risk. With the introduction of pharmacotherapies for hATTR amyloidosis with polyneuropathy, liver transplantation is rarely a first-level treatment.

Other Organ Transplants

Since the amyloid deposits that accumulate with hATTR-PN have the potential to damage other tissue and organs, transplantation of affected organs, such as a heart or kidneys, may be advised.

Prognosis and Easier Ways to Cope

Research indicates that people with hATTR-PN typically require assistance with walking after five to six years and have alife expectancyof seven to 10 years from the onset of neuropathy. However, recently approved treatments are changing the natural history of this progressive disorder. Early diagnosis can lead to earlier treatment with therapies that show improved outcomes.

Living with hATTR-PN can be challenging. The pain and numbness accompanying nerve damage can make it harder to continue your everyday activities as nerve damage worsens.

Talk to your healthcare provider about ways that can make it easier to cope with this disease and whether the following strategies can work for you:

Assistive Devices and Orthotics

Summary

Hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) is a rare disease that is passed from parent to child. It occurs when a damaged gene changes the space and function of the protein transthyretin. The change causes the gene to misfold and form clusters of amyloid deposits that damage your nerves.

The impact of hATTR-PN can be severe as symptoms of pain and numbness prevent you from doing daily tasks. Without treatment, nerve damage can progress to the degree that you need a wheelchair.

However, early diagnosis is key to getting better outcomes for this disease. Novel treatments can reduce symptoms, improve quality of life, and slow disease progression for many people.

Know your risk factors for hATTR-PN so you can get an early diagnosis. This can help you and your family improve your outcomes with this severe disease.

17 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Vélez-Santamaría V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C.Hereditary transthyretin amyloidosis with polyneuropathy: monitoring and management.Int J Gen Med. 2022;15:8677-8684. doi:10.2147/IJGM.S338430Adams D, Ando Y, Beirão JM, et al.Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.J Neurol. 2021;268(6):2109-2122. doi:10.1007/s00415-019-09688-0Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M.Diagnosis and treatment of hereditary transthyretin amyloidosis (Hattr) polyneuropathy: current perspectives on improving patient care.Ther Clin Risk Manag. 2020;16:109-123. doi:10.2147/TCRM.S219979Vélez-Santamaría V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C.Hereditary transthyretin amyloidosis with polyneuropathy: monitoring and management.Int J Gen Med. 2022;15:8677-8684. doi:10.7861/clinmedicine.18-2-s30Amyloidosis Research Consortium.Hereditary transthyretin amyloidosis.Amyloidosis Research Consortium.Hereditary ATTR amyloidosis.Juarez M, Del Rio-Pertuz G, Parmar K, et al.A case of early hereditary transthyretin amyloid cardiomyopathy recognition with genetic screening: a case report.J Prim Care Community Health. 2022;13:21501319211062682. doi:10.1177/21501319211062682Tozza S, Severi D, Spina E, et al.The neuropathy in hereditary transthyretin amyloidosis: a narrative review.J Peripher Nerv Syst. 2021;26(2):155-159. doi:10.1111/jns.12451Barroso FA, Coelho T, Dispenzieri A, et al.Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS).Amyloid. 2022 Sep;29(3):175-183. doi:10.1080/13506129.2022.2043270National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).Amyloidosis and kidney disease.Amyloidosis Research Consortium.Disease overview: hereditary transthyretin amyloidosis.Amyloidosis Research Consortium.Treatment overview: hereditary transthyretin amyloidosis.Ericzon BG, Wilczek HE, Larsson M, et al.Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative?Transplantation. 2015;99(9):1847-1854. doi:10.1097/TP.0000000000000574Živkovic‘ SA.Neuropathy associated with hereditary transthyretin amyloidosis—diagnosis and management.US Neurology. 2020;16(2):103–9. doi:10.17925/USN.2020.16.2.103Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A, et al.Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta‐analysis.European J of Heart Fail. 2022;24(9):1677-1696. doi:10.1002/ejhf.2589Waddington-Cruz M, Wixner J, Amass L, Kiszko J, Chapman D, Ando Y.Characteristics of patients with late- vs. Early-onset val30met transthyretin amyloidosis from the transthyretin amyloidosis outcomes survey(Thaos).Neurol Ther. 2021;10(2):753-766. doi:10.1007/s40120-021-00258-zAmyloidosis Research Consortium.Neuropathy in amyloidosis.

17 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Vélez-Santamaría V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C.Hereditary transthyretin amyloidosis with polyneuropathy: monitoring and management.Int J Gen Med. 2022;15:8677-8684. doi:10.2147/IJGM.S338430Adams D, Ando Y, Beirão JM, et al.Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.J Neurol. 2021;268(6):2109-2122. doi:10.1007/s00415-019-09688-0Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M.Diagnosis and treatment of hereditary transthyretin amyloidosis (Hattr) polyneuropathy: current perspectives on improving patient care.Ther Clin Risk Manag. 2020;16:109-123. doi:10.2147/TCRM.S219979Vélez-Santamaría V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C.Hereditary transthyretin amyloidosis with polyneuropathy: monitoring and management.Int J Gen Med. 2022;15:8677-8684. doi:10.7861/clinmedicine.18-2-s30Amyloidosis Research Consortium.Hereditary transthyretin amyloidosis.Amyloidosis Research Consortium.Hereditary ATTR amyloidosis.Juarez M, Del Rio-Pertuz G, Parmar K, et al.A case of early hereditary transthyretin amyloid cardiomyopathy recognition with genetic screening: a case report.J Prim Care Community Health. 2022;13:21501319211062682. doi:10.1177/21501319211062682Tozza S, Severi D, Spina E, et al.The neuropathy in hereditary transthyretin amyloidosis: a narrative review.J Peripher Nerv Syst. 2021;26(2):155-159. doi:10.1111/jns.12451Barroso FA, Coelho T, Dispenzieri A, et al.Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS).Amyloid. 2022 Sep;29(3):175-183. doi:10.1080/13506129.2022.2043270National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).Amyloidosis and kidney disease.Amyloidosis Research Consortium.Disease overview: hereditary transthyretin amyloidosis.Amyloidosis Research Consortium.Treatment overview: hereditary transthyretin amyloidosis.Ericzon BG, Wilczek HE, Larsson M, et al.Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative?Transplantation. 2015;99(9):1847-1854. doi:10.1097/TP.0000000000000574Živkovic‘ SA.Neuropathy associated with hereditary transthyretin amyloidosis—diagnosis and management.US Neurology. 2020;16(2):103–9. doi:10.17925/USN.2020.16.2.103Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A, et al.Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta‐analysis.European J of Heart Fail. 2022;24(9):1677-1696. doi:10.1002/ejhf.2589Waddington-Cruz M, Wixner J, Amass L, Kiszko J, Chapman D, Ando Y.Characteristics of patients with late- vs. Early-onset val30met transthyretin amyloidosis from the transthyretin amyloidosis outcomes survey(Thaos).Neurol Ther. 2021;10(2):753-766. doi:10.1007/s40120-021-00258-zAmyloidosis Research Consortium.Neuropathy in amyloidosis.

Vélez-Santamaría V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C.Hereditary transthyretin amyloidosis with polyneuropathy: monitoring and management.Int J Gen Med. 2022;15:8677-8684. doi:10.2147/IJGM.S338430Adams D, Ando Y, Beirão JM, et al.Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.J Neurol. 2021;268(6):2109-2122. doi:10.1007/s00415-019-09688-0Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M.Diagnosis and treatment of hereditary transthyretin amyloidosis (Hattr) polyneuropathy: current perspectives on improving patient care.Ther Clin Risk Manag. 2020;16:109-123. doi:10.2147/TCRM.S219979Vélez-Santamaría V, Nedkova-Hristova V, Morales de la Prida M, Casasnovas C.Hereditary transthyretin amyloidosis with polyneuropathy: monitoring and management.Int J Gen Med. 2022;15:8677-8684. doi:10.7861/clinmedicine.18-2-s30Amyloidosis Research Consortium.Hereditary transthyretin amyloidosis.Amyloidosis Research Consortium.Hereditary ATTR amyloidosis.Juarez M, Del Rio-Pertuz G, Parmar K, et al.A case of early hereditary transthyretin amyloid cardiomyopathy recognition with genetic screening: a case report.J Prim Care Community Health. 2022;13:21501319211062682. doi:10.1177/21501319211062682Tozza S, Severi D, Spina E, et al.The neuropathy in hereditary transthyretin amyloidosis: a narrative review.J Peripher Nerv Syst. 2021;26(2):155-159. doi:10.1111/jns.12451Barroso FA, Coelho T, Dispenzieri A, et al.Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS).Amyloid. 2022 Sep;29(3):175-183. doi:10.1080/13506129.2022.2043270National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).Amyloidosis and kidney disease.Amyloidosis Research Consortium.Disease overview: hereditary transthyretin amyloidosis.Amyloidosis Research Consortium.Treatment overview: hereditary transthyretin amyloidosis.Ericzon BG, Wilczek HE, Larsson M, et al.Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative?Transplantation. 2015;99(9):1847-1854. doi:10.1097/TP.0000000000000574Živkovic‘ SA.Neuropathy associated with hereditary transthyretin amyloidosis—diagnosis and management.US Neurology. 2020;16(2):103–9. doi:10.17925/USN.2020.16.2.103Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A, et al.Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta‐analysis.European J of Heart Fail. 2022;24(9):1677-1696. doi:10.1002/ejhf.2589Waddington-Cruz M, Wixner J, Amass L, Kiszko J, Chapman D, Ando Y.Characteristics of patients with late- vs. Early-onset val30met transthyretin amyloidosis from the transthyretin amyloidosis outcomes survey(Thaos).Neurol Ther. 2021;10(2):753-766. doi:10.1007/s40120-021-00258-zAmyloidosis Research Consortium.Neuropathy in amyloidosis.

Adams D, Ando Y, Beirão JM, et al.Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.J Neurol. 2021;268(6):2109-2122. doi:10.1007/s00415-019-09688-0

Luigetti M, Romano A, Di Paolantonio A, Bisogni G, Sabatelli M.Diagnosis and treatment of hereditary transthyretin amyloidosis (Hattr) polyneuropathy: current perspectives on improving patient care.Ther Clin Risk Manag. 2020;16:109-123. doi:10.2147/TCRM.S219979

Amyloidosis Research Consortium.Hereditary transthyretin amyloidosis.

Amyloidosis Research Consortium.Hereditary ATTR amyloidosis.

Juarez M, Del Rio-Pertuz G, Parmar K, et al.A case of early hereditary transthyretin amyloid cardiomyopathy recognition with genetic screening: a case report.J Prim Care Community Health. 2022;13:21501319211062682. doi:10.1177/21501319211062682

Tozza S, Severi D, Spina E, et al.The neuropathy in hereditary transthyretin amyloidosis: a narrative review.J Peripher Nerv Syst. 2021;26(2):155-159. doi:10.1111/jns.12451

Barroso FA, Coelho T, Dispenzieri A, et al.Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS).Amyloid. 2022 Sep;29(3):175-183. doi:10.1080/13506129.2022.2043270

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).Amyloidosis and kidney disease.

Amyloidosis Research Consortium.Disease overview: hereditary transthyretin amyloidosis.

Amyloidosis Research Consortium.Treatment overview: hereditary transthyretin amyloidosis.

Ericzon BG, Wilczek HE, Larsson M, et al.Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative?Transplantation. 2015;99(9):1847-1854. doi:10.1097/TP.0000000000000574

Živkovic‘ SA.Neuropathy associated with hereditary transthyretin amyloidosis—diagnosis and management.US Neurology. 2020;16(2):103–9. doi:10.17925/USN.2020.16.2.103

Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A, et al.Prevalence and clinical outcomes of transthyretin amyloidosis: a systematic review and meta‐analysis.European J of Heart Fail. 2022;24(9):1677-1696. doi:10.1002/ejhf.2589

Waddington-Cruz M, Wixner J, Amass L, Kiszko J, Chapman D, Ando Y.Characteristics of patients with late- vs. Early-onset val30met transthyretin amyloidosis from the transthyretin amyloidosis outcomes survey(Thaos).Neurol Ther. 2021;10(2):753-766. doi:10.1007/s40120-021-00258-z

Amyloidosis Research Consortium.Neuropathy in amyloidosis.

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hATTR Amyloidosis and Polyneuropathy Symptoms#

Treatment to Manage hATTR Amyloidosis With Polyneuropathy#

Drug Treatments#

Liver Transplant#

Other Organ Transplants#

Prognosis and Easier Ways to Cope#

Summary#