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transthyretin amyloidosis
ICD-10 Codes
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Description
Transthyretin amyloidosis, also known as ATTR amyloidosis, is a progressive condition characterized by the buildup of abnormal protein deposits called amyloids in various organs and tissues of the body.
Causes and Types
- The condition is caused by a misfolded transthyretin (TTR) protein that forms into fibrous clumps, leading to the development of amyloid fibrils [1].
- There are two main types of ATTR amyloidosis: hereditary and wild-type.
- Hereditary ATTR amyloidosis is caused by a fault or mutation in the transthyretin (TTR) gene, which is inherited and runs in families [6].
- Wild-type ATTR amyloidosis occurs when the TTR protein naturally ages and misfolds, leading to amyloid formation.
Symptoms and Complications
- The condition can affect various organs and tissues, including the heart, nerves, kidneys, and digestive system.
- Symptoms may include:
- Cardiac symptoms: shortness of breath, fatigue, swelling in the legs and feet [8].
- Neurological symptoms: numbness or tingling in the hands and feet, weakness or paralysis [7].
- Gastrointestinal symptoms: abdominal pain, diarrhea, constipation.
- If left untreated, ATTR amyloidosis can lead to serious complications, including heart failure, kidney disease, and neuropathy.
References
[1] Transthyretin amyloidosis is caused by a protein called transthyretin, or TTR, that changes its shape and forms into fibrous clumps. [6] Hereditary ATTR amyloidosis is caused by a fault or mutation in the transthyretin (TTR) gene which is inherited i.e. runs in families. [7] Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is characterized by a slowly progressive peripheral sensorimotor and/or autonomic neuropathy. [8] Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed and potentially fatal disease of the heart muscle.
Additional Characteristics
- heart failure
- kidney disease
- Transthyretin amyloidosis
- misfolded transthyretin (TTR) protein
- hereditary ATTR amyloidosis
- wild-type ATTR amyloidosis
- neuropathy
- transthyretin amyloid cardiomyopathy
Signs and Symptoms
Transthyretin amyloidosis (ATTR-CM) is a condition characterized by the buildup of faulty proteins (fibrils) on the heart or nerves, leading to various symptoms.
Common symptoms:
- Cardiomyopathy and heart failure [1]
- Enlarged tongue
- Severe fatigue and weakness
- Shortness of breath
- Numbness, tingling, or pain in the hands or feet
- Swelling of the ankles and legs
These symptoms can progress rapidly, with some individuals experiencing a sharp drop in blood pressure, diarrhea, constipation, problems with urination, and muscle weakness [4][5].
Additional symptoms:
- Back pain
- Shoulder, knee, or hip pain
- Trigger finger
- Carpal tunnel syndrome
- Muscle weakness
The amyloid build-up can also affect involuntary body functions, such as blood pressure, heart rate, and digestion [7]. In some cases, ATTR-CM may present with symptoms of heart failure, including fatigue, shortness of breath, and peripheral edema [
Additional Symptoms
- Trigger finger
- Shortness of breath
- Carpal tunnel syndrome
- Enlarged tongue
- Severe fatigue and weakness
- Numbness, tingling, or pain in the hands or feet
- Swelling of the ankles and legs
- Shoulder, knee, or hip pain
- Problems with urination
- muscle weakness
- heart failure
- diarrhea
- pain
- constipation
Diagnostic Tests
Transthyretin amyloidosis (ATTR) diagnosis involves a combination of tests to confirm the presence of the disease. Here are some diagnostic tests for ATTR:
- DNA testing: This is the first step in diagnosing ATTR, as it helps identify the genetic mutation responsible for the condition [1].
- Biopsy: A tissue biopsy can be used to diagnose ATTR, particularly if there's a suspicion of cardiac involvement [3]. The biopsy involves taking a sample of tissue from the heart or other affected areas.
- Amyloid typing: This test is used to confirm the presence of amyloid deposits in the body and determine their composition [1].
- Electrocardiogram (ECG): An ECG can help identify cardiac involvement in ATTR, although it's not a definitive diagnostic tool [2].
- Cardiac imaging: Tests like echocardiograms, MRIs, and positron emission tomography (PET) scans can help assess cardiac function and detect amyloid deposits [2].
- Nuclear PYP scan: This test involves injecting a radioactive dye that accumulates in areas with amyloid deposits, making them visible on an image [3].
- Mass spectrometry: This test is used to evaluate the structure of transthyretin (TTR) protein and identify any structural changes associated with ATTR [6].
- NT-proBNP testing: Elevated levels of NT-proBNP can indicate early cardiac involvement in ATTR, even before symptoms appear [7].
It's essential to note that a combination of these tests is often used to confirm the diagnosis of ATTR. A healthcare professional will determine the most appropriate diagnostic approach based on individual patient needs.
References: [1] Mar 27, 2024 — The complete workup for transthyretin-related amyloidosis (ATTR) should include DNA testing, biopsy, and amyloid typing. [2] How is transthyretin amyloidosis (ATTR-CM) diagnosed? · Electrocardiogram (ECG). · Cardiac imaging like echocardiograms, MRIs and positron emission tomography ( ... [3] ATTR can be diagnosed by biopsy diagnosis or by nonbiopsy diagnosis with a nuclear PYP scan (high uptake of PYP in patients with ATTR in patients with a ... [6] Mass spectrometry to evaluate transthyretin (TTR) protein structure is performed first. In all cases demonstrating a structural change, the TTR gene will be ... [7] by MS Maurer · 2019 · Cited by 493 — NT-proBNP is a biomarker that is elevated early in ATTRm amyloidosis before cardiac symptoms appear, especially among asymptomatic carriers of a ...
Additional Diagnostic Tests
- Biopsy
- Electrocardiogram (ECG)
- DNA testing
- Mass spectrometry
- Amyloid typing
- Cardiac imaging
- Nuclear PYP scan
- NT-proBNP testing
Treatment
Transthyretin amyloidosis, also known as TTR amyloidosis, is a progressive disease that affects various organs and tissues in the body. The good news is that there are several effective drug treatments available to manage this condition.
Newer drugs for TTR amyloidosis
Recent studies have shown that newer drugs such as tafamidis, patisiran (Onpattro), vutrisiran (Amvuttra), inotersen (Tegsedi), and eplontersen (Waiuna) can be used to stop or reverse the progression of polyneuropathy, a common complication of TTR amyloidosis [1]. These drugs work by stabilizing the tetramer of TTR protein, preventing its misfolding and aggregation into amyloid fibrils.
Specific treatments for TTR amyloidosis
- Tafamidis: This is a selective TTR stabilizer that works by binding to TTR protein to prevent misfolding [9]. It has been shown to slow disease progression in patients with TTR cardiac amyloidosis [7].
- Patisiran (Onpattro): This siRNA agent reduces serum transthyretin (TTR) protein and TTR protein deposits in tissues, making it an effective treatment for TTR cardiac amyloidosis [5].
- Inotersen (Tegsedi): This drug has been shown to reduce TTR protein levels and slow disease progression in patients with TTR amyloidosis [4].
Other treatments under investigation
Researchers are also exploring other potential treatments, such as diflunisal, a non-steroidal anti-inflammatory drug that stabilizes the tetramer of TTR protein [3]. Green tea, tolcapone, and other agents have also been studied for their potential therapeutic effects in TTR amyloidosis.
Conclusion
In conclusion, there are several effective drug treatments available to manage transthyretin amyloidosis. These newer drugs offer hope for patients with this progressive disease, and ongoing research is likely to uncover even more promising therapies in the future.
References:
[1] Context 2 [3] Context 3 [4] Context 4 [5] Context 5 [7] Context 7 [9] Context 9
Recommended Medications
- patisiran (Onpattro)
- vutrisiran (Amvuttra)
- inotersen (Tegsedi)
- eplontersen (Waiuna)
- tafamidis
- diflunisal
- Diflunisal
💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.
Differential Diagnosis
Transthyretin Amyloidosis Differential Diagnosis
Transthyretin (TTR) amyloidosis, also known as ATTR amyloidosis, is a disease caused by the accumulation of abnormal TTR protein fibrils in various tissues and organs. The differential diagnosis of TTR amyloidosis involves considering other conditions that may present with similar clinical features.
Conditions to Consider
- Hereditary transthyretin-related amyloidosis (ATTR): This is the most common form of TTR amyloidosis, caused by mutations in the TTR gene. It can be inherited or sporadic.
- Wild-type transthyretin amyloidosis (WT-ATTR): This form of TTR amyloidosis occurs in individuals without any known genetic mutation.
- Chronic inflammatory demyelinating polyneuropathy (CIDP): A rare autoimmune disorder that can cause nerve damage and symptoms similar to those seen in TTR amyloidosis.
- Lumbar spinal stenosis: A condition characterized by narrowing of the lumbar spine, which can lead to neurological symptoms.
Diagnostic Considerations
When diagnosing TTR amyloidosis, it is essential to consider these conditions as part of the differential diagnosis. This involves a comprehensive diagnostic workup, including:
- Imaging studies: Such as MRI or CT scans to rule out other conditions that may cause similar symptoms.
- Histopathology: A biopsy of affected tissues can help confirm the presence of amyloid deposits and identify the type of amyloidosis.
- Genetic testing: To determine if a genetic mutation is present, which can be helpful in diagnosing hereditary ATTR.
References
- [1] by C Rapezzi · 2013 · Cited by 360 — Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic ...
- [5] by C Rapezzi · 2013 · Cited by 360 — Aims: Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and ...
- [8] by MS Maurer · 2019 · Cited by 492 — Transthyretin amyloidosis (ATTR) is a disease caused by abnormal fibrils derived from TTR (transthyretin), a protein produced mainly by the ...
Additional Differential Diagnoses
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Hereditary transthyretin-related amyloidosis (ATTR)
- Wild-type transthyretin amyloidosis (WT-ATTR)
- Lumbar spinal stenosis
Additional Information
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- An amyloidosis that is characterized by a loss of sensation in the extremities, cardiomyopathy, nephropathy, vitreous opacities, and CNS amyloidosis resulting from abnormal deposits of amyloid protein in the body's organs and tissues and has_material_basis_in autosomal dominant inheritance of mutations in the TTR gene.
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