Transthyretin-related amyloidosis is a rare disease, it is a progressive disease. It is caused by accumulation of abnormal transthyretin (TTR) protein in many tissues and organs. Transthyretin is produced by liver and transfers vitamin A and thyroid hormones. There are 2 types of ATTR amyloidosis i.e., Wild-type ATTR amyloidosis and hereditary ATTR amyloidosis.
Hereditary ATTR amyloidosis (hATTR) involves mutations in the transthyretin gene that causes hereditary ATTR amyloidosis. It is an inherited autosomal dominant disease. Atypical transthyretin protein is produced when there is a mutation in the transthyretin gene. This can lead to abnormal production of amyloid in brain, heart, and other organs.
Wild-type ATTR amyloidosis is caused by a misfolding of transthyretin protein. It leads to the formation of abnormal amyloid in many tissues and organs. manily it is caused by aging instead of genetic changes.
Epidemiology
There are many significant variations in the prevalence and incidence of hTTR amyloidosis from different groups and geographical regions. Specific gene variants are present at a high rate in some ethnic groups pr geographical areas.
Age related rises in the incidence of wtATTR suggest that the disease is primarily affects the elderly with the majority cases are diagnosed in individuals whose age is over 60.
The symptoms like neuropathy and heart failure are easily misinterpreted for other aging disorders.
Anatomy
Pathophysiology
Mutant transthyretin proteinare caused by mutations in te gene of transthyretin. This leads to misfolding of genes and this type of mutation can lead to hereditary ATTR amyloidosis. Individuals who are >60 years have misfolding of transthyretin gene. The affected tissues and organs may have abnormal function and structure damage due to accumulation of amyloid.
Etiology
Transthyretin proteins can misfold and form amyloid fibrils. The inheritance pattern for hATTR amyloidosis is autosomal dominant. One inherited copy of the defective gene from each parent will be affected with this condition.
Genetics
Prognostic Factors
The course and degree of hATTR amyloidosis may be affected by the mutations in the TTR gene. A few mutations can have mild symptoms and a later others are associated with more aggressive disease and the earlier symptoms are continue.
The functional condition of patient may have affected the result at the time of diagnosis. Those individuals who have mild symptoms and preserved the organ function are far away better than those who have severe and aggressive impairments to their functional capacity of organs.
Symptomatic cardiac involvement in ATTR does not always predict a negative prognosis, unlike light chain amyloidosis.
Clinical History
In ATTR amyloidosis, there is cardiac involvement. It prevents and can lead to result in arrhythmias, conduction problems, and heart failure. hATTRbeginin the adulthoods between the age of 30 years to 80 years. It depends on the particular gene mutations.
Physical Examination
The physical examination of ATTR includes neurological, cardiovascular, and musculoskeletal examination.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
The particular genetic mutation in hTTR can affect the age of onset and severity of symptoms.
wtATTR amyloidosis occurs over the age of 60. This is age-related misfolding of normal TTR protein
The treatment of renal involvement in ATTR amyloidosis includes control blood pressure, optimize the glycemic control, and address complications like nephrotic syndrome, proteinuria, and renal impairment.
Dietary counseling and nutritional support can be beneficial to patients who have ATTR amyloidosis, specifically those who have malnutrition or weight loss because of gastrointestinal involvement or other complications.
A balanced diet which is rich in whole grains, vegetables, fruits, and low saturated fats can control the symptoms of heart failure and maintain heart function.
Individuals who have peripheral neuropathy or other disease that limit their mobility creating any changes in their environment in home can help to increase the accessibility and safety.
Regular exercise, adjust to each individual’s limitations and capabilities may support to preserve the muscle mass, general wellbeing and cardiovascular health.
Use of small interfering RNA agents
Patisiran: It is a small interfering RNA (siRNA) agent that inhibits TTR gene expression at mRNA level.
Inotersen:It targets the expression of the TTR gene and reduces the levels of TTR by improving neurological symptoms in hATTR polyneuropathy.
Use of Cardiovascular to treat Transthyretin-Related Amyloidosis
Tafamidis:Tafamidis binds to the thyroxine binding site of TTR molecules. It stabilizes the tetrameric structure and prevents their dissociation into the monomer. It reduces the formation rate of amyloid fibril.
Nerve Decompression Surgery: It is used to relive the pressure on the affected nerve and lower the symptoms. Nerve decompression surgery can be performed in specific cases of peripheral neuropathy caused by amyloid deposition.
Renal Biopsy: When ATTR amyloidosis is associated with renal impairment in individuals, a renal biopsy can be performed for histological assessment.
Vitrectomy: Patients who have vitreous can get benefit from vitrectomy. retinal pigment epithelial cells and ciliary pigment epithelial cells are known to produce TTR locally. The development of ocular disease indicates that intraocular TTR generation continues after liver transplantation.
The identification of symptoms and indications that lead to ATTR amyloidosis which can involve gastrointestinal, neurological at the beginning.
Supportive care treatment, pharmaceutical agents for neurological, cardiac, gastrointestinal, renal can be used to treat the symptoms and improve the quality of life.
To check the treatment response and make necessary management in the treatment, a regular monitoring which involve clinical assessment, laboratory test, imaging studies, and function testing is necessary.
Administer a dose of 284 mg subcutaneously once in a week and then administer on the same day every week Dosage Modifications Platelets
Don’t start if <100x 10^9/L
If platelet count ≥100x 10^9/L then continue with weekly dose
If platelet count <25x 10^9/L then monitor daily till two successive values are >25 and then two times in a week till three successive values are >75
If platelet count ≥75 to <100 x 10^9/L then stop treatment and it may resume if platelet count >100 Urine protein to creatinine ratio (UPCR)
For UPCR ≥2000 mg/g: conduct further evaluation for acute glomerulonephritis
If acute glomerulonephritis confirmed, discontinue it forever Renal impairment
Mild-to-moderate: dose modification not required
Severe: study not performed Hepatic impairment
Mild: dose modification not required
Moderate-to-severe: study not performed Dosing Considerations
Observe AST, ALT, and total bilirubin in every four months
Observe serum creatinine, urinalysis, eGFR and UPCR in every two weeks
Transthyretin-related amyloidosis is a rare disease, it is a progressive disease. It is caused by accumulation of abnormal transthyretin (TTR) protein in many tissues and organs. Transthyretin is produced by liver and transfers vitamin A and thyroid hormones. There are 2 types of ATTR amyloidosis i.e., Wild-type ATTR amyloidosis and hereditary ATTR amyloidosis.
Hereditary ATTR amyloidosis (hATTR) involves mutations in the transthyretin gene that causes hereditary ATTR amyloidosis. It is an inherited autosomal dominant disease. Atypical transthyretin protein is produced when there is a mutation in the transthyretin gene. This can lead to abnormal production of amyloid in brain, heart, and other organs.
Wild-type ATTR amyloidosis is caused by a misfolding of transthyretin protein. It leads to the formation of abnormal amyloid in many tissues and organs. manily it is caused by aging instead of genetic changes.
There are many significant variations in the prevalence and incidence of hTTR amyloidosis from different groups and geographical regions. Specific gene variants are present at a high rate in some ethnic groups pr geographical areas.
Age related rises in the incidence of wtATTR suggest that the disease is primarily affects the elderly with the majority cases are diagnosed in individuals whose age is over 60.
The symptoms like neuropathy and heart failure are easily misinterpreted for other aging disorders.
Mutant transthyretin proteinare caused by mutations in te gene of transthyretin. This leads to misfolding of genes and this type of mutation can lead to hereditary ATTR amyloidosis. Individuals who are >60 years have misfolding of transthyretin gene. The affected tissues and organs may have abnormal function and structure damage due to accumulation of amyloid.
Transthyretin proteins can misfold and form amyloid fibrils. The inheritance pattern for hATTR amyloidosis is autosomal dominant. One inherited copy of the defective gene from each parent will be affected with this condition.
The course and degree of hATTR amyloidosis may be affected by the mutations in the TTR gene. A few mutations can have mild symptoms and a later others are associated with more aggressive disease and the earlier symptoms are continue.
The functional condition of patient may have affected the result at the time of diagnosis. Those individuals who have mild symptoms and preserved the organ function are far away better than those who have severe and aggressive impairments to their functional capacity of organs.
Symptomatic cardiac involvement in ATTR does not always predict a negative prognosis, unlike light chain amyloidosis.
In ATTR amyloidosis, there is cardiac involvement. It prevents and can lead to result in arrhythmias, conduction problems, and heart failure. hATTRbeginin the adulthoods between the age of 30 years to 80 years. It depends on the particular gene mutations.
The physical examination of ATTR includes neurological, cardiovascular, and musculoskeletal examination.
The particular genetic mutation in hTTR can affect the age of onset and severity of symptoms.
wtATTR amyloidosis occurs over the age of 60. This is age-related misfolding of normal TTR protein
The treatment of renal involvement in ATTR amyloidosis includes control blood pressure, optimize the glycemic control, and address complications like nephrotic syndrome, proteinuria, and renal impairment.
Dietary counseling and nutritional support can be beneficial to patients who have ATTR amyloidosis, specifically those who have malnutrition or weight loss because of gastrointestinal involvement or other complications.
Neurology
Rheumatology
A balanced diet which is rich in whole grains, vegetables, fruits, and low saturated fats can control the symptoms of heart failure and maintain heart function.
Individuals who have peripheral neuropathy or other disease that limit their mobility creating any changes in their environment in home can help to increase the accessibility and safety.
Regular exercise, adjust to each individual’s limitations and capabilities may support to preserve the muscle mass, general wellbeing and cardiovascular health.
Rheumatology
Patisiran: It is a small interfering RNA (siRNA) agent that inhibits TTR gene expression at mRNA level.
Inotersen:It targets the expression of the TTR gene and reduces the levels of TTR by improving neurological symptoms in hATTR polyneuropathy.
Rheumatology
Tafamidis:Tafamidis binds to the thyroxine binding site of TTR molecules. It stabilizes the tetrameric structure and prevents their dissociation into the monomer. It reduces the formation rate of amyloid fibril.
Rheumatology
Surgery, General
Nerve Decompression Surgery: It is used to relive the pressure on the affected nerve and lower the symptoms. Nerve decompression surgery can be performed in specific cases of peripheral neuropathy caused by amyloid deposition.
Renal Biopsy: When ATTR amyloidosis is associated with renal impairment in individuals, a renal biopsy can be performed for histological assessment.
Vitrectomy: Patients who have vitreous can get benefit from vitrectomy. retinal pigment epithelial cells and ciliary pigment epithelial cells are known to produce TTR locally. The development of ocular disease indicates that intraocular TTR generation continues after liver transplantation.
Physical Medicine and Rehabilitation
The identification of symptoms and indications that lead to ATTR amyloidosis which can involve gastrointestinal, neurological at the beginning.
Supportive care treatment, pharmaceutical agents for neurological, cardiac, gastrointestinal, renal can be used to treat the symptoms and improve the quality of life.
To check the treatment response and make necessary management in the treatment, a regular monitoring which involve clinical assessment, laboratory test, imaging studies, and function testing is necessary.
Transthyretin-related amyloidosis is a rare disease, it is a progressive disease. It is caused by accumulation of abnormal transthyretin (TTR) protein in many tissues and organs. Transthyretin is produced by liver and transfers vitamin A and thyroid hormones. There are 2 types of ATTR amyloidosis i.e., Wild-type ATTR amyloidosis and hereditary ATTR amyloidosis.
Hereditary ATTR amyloidosis (hATTR) involves mutations in the transthyretin gene that causes hereditary ATTR amyloidosis. It is an inherited autosomal dominant disease. Atypical transthyretin protein is produced when there is a mutation in the transthyretin gene. This can lead to abnormal production of amyloid in brain, heart, and other organs.
Wild-type ATTR amyloidosis is caused by a misfolding of transthyretin protein. It leads to the formation of abnormal amyloid in many tissues and organs. manily it is caused by aging instead of genetic changes.
There are many significant variations in the prevalence and incidence of hTTR amyloidosis from different groups and geographical regions. Specific gene variants are present at a high rate in some ethnic groups pr geographical areas.
Age related rises in the incidence of wtATTR suggest that the disease is primarily affects the elderly with the majority cases are diagnosed in individuals whose age is over 60.
The symptoms like neuropathy and heart failure are easily misinterpreted for other aging disorders.
Mutant transthyretin proteinare caused by mutations in te gene of transthyretin. This leads to misfolding of genes and this type of mutation can lead to hereditary ATTR amyloidosis. Individuals who are >60 years have misfolding of transthyretin gene. The affected tissues and organs may have abnormal function and structure damage due to accumulation of amyloid.
Transthyretin proteins can misfold and form amyloid fibrils. The inheritance pattern for hATTR amyloidosis is autosomal dominant. One inherited copy of the defective gene from each parent will be affected with this condition.
The course and degree of hATTR amyloidosis may be affected by the mutations in the TTR gene. A few mutations can have mild symptoms and a later others are associated with more aggressive disease and the earlier symptoms are continue.
The functional condition of patient may have affected the result at the time of diagnosis. Those individuals who have mild symptoms and preserved the organ function are far away better than those who have severe and aggressive impairments to their functional capacity of organs.
Symptomatic cardiac involvement in ATTR does not always predict a negative prognosis, unlike light chain amyloidosis.
In ATTR amyloidosis, there is cardiac involvement. It prevents and can lead to result in arrhythmias, conduction problems, and heart failure. hATTRbeginin the adulthoods between the age of 30 years to 80 years. It depends on the particular gene mutations.
The physical examination of ATTR includes neurological, cardiovascular, and musculoskeletal examination.
The particular genetic mutation in hTTR can affect the age of onset and severity of symptoms.
wtATTR amyloidosis occurs over the age of 60. This is age-related misfolding of normal TTR protein
The treatment of renal involvement in ATTR amyloidosis includes control blood pressure, optimize the glycemic control, and address complications like nephrotic syndrome, proteinuria, and renal impairment.
Dietary counseling and nutritional support can be beneficial to patients who have ATTR amyloidosis, specifically those who have malnutrition or weight loss because of gastrointestinal involvement or other complications.
Neurology
Rheumatology
A balanced diet which is rich in whole grains, vegetables, fruits, and low saturated fats can control the symptoms of heart failure and maintain heart function.
Individuals who have peripheral neuropathy or other disease that limit their mobility creating any changes in their environment in home can help to increase the accessibility and safety.
Regular exercise, adjust to each individual’s limitations and capabilities may support to preserve the muscle mass, general wellbeing and cardiovascular health.
Rheumatology
Patisiran: It is a small interfering RNA (siRNA) agent that inhibits TTR gene expression at mRNA level.
Inotersen:It targets the expression of the TTR gene and reduces the levels of TTR by improving neurological symptoms in hATTR polyneuropathy.
Rheumatology
Tafamidis:Tafamidis binds to the thyroxine binding site of TTR molecules. It stabilizes the tetrameric structure and prevents their dissociation into the monomer. It reduces the formation rate of amyloid fibril.
Rheumatology
Surgery, General
Nerve Decompression Surgery: It is used to relive the pressure on the affected nerve and lower the symptoms. Nerve decompression surgery can be performed in specific cases of peripheral neuropathy caused by amyloid deposition.
Renal Biopsy: When ATTR amyloidosis is associated with renal impairment in individuals, a renal biopsy can be performed for histological assessment.
Vitrectomy: Patients who have vitreous can get benefit from vitrectomy. retinal pigment epithelial cells and ciliary pigment epithelial cells are known to produce TTR locally. The development of ocular disease indicates that intraocular TTR generation continues after liver transplantation.
Physical Medicine and Rehabilitation
The identification of symptoms and indications that lead to ATTR amyloidosis which can involve gastrointestinal, neurological at the beginning.
Supportive care treatment, pharmaceutical agents for neurological, cardiac, gastrointestinal, renal can be used to treat the symptoms and improve the quality of life.
To check the treatment response and make necessary management in the treatment, a regular monitoring which involve clinical assessment, laboratory test, imaging studies, and function testing is necessary.
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