4 free views remaining today

transthyretin amyloidosis

ICD-10 Codes

Related ICD-10:

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

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

💊 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

rdf-schema#domain
https://w3id.org/def/predibionto#has_symptom_675
owl#annotatedSource
t332229
oboInOwl#hasOBONamespace
disease_ontology
rdf-schema#comment
OMIM mapping confirmed by DO. [SN].
oboInOwl#id
DOID:0050638
core#notation
DOID:0050638
oboInOwl#hasAlternativeId
DOID:0050761
oboInOwl#hasDbXref
ORDO:85447
oboInOwl#hasExactSynonym
TTR amyloidosis
rdf-schema#label
transthyretin amyloidosis
IAO_0000115
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.
rdf-schema#subClassOf
t332351
oboInOwl#inSubset
http://purl.obolibrary.org/obo/doid#DO_rare_slim
IDO_0000664
http://purl.obolibrary.org/obo/GENO_0000147
RO_0004026
http://purl.obolibrary.org/obo/UBERON_0001021
relatedICD
http://example.org/icd10/E85.82
22-rdf-syntax-ns#type
http://www.w3.org/2002/07/owl#Class

Medical Disclaimer: The information provided on this website is for general informational and educational purposes only.

It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with questions about your medical condition.