Wild-type transthyretin amyloid (WTTA), also known as senile systemic amyloidosis (SSA),
transthyretin-related hereditary amyloidosis where a genetically mutated transthyretin
protein tends to deposit much earlier than in WTTA due to abnormal conformation and bioprocessing.
It belongs to a group of diseases called amyloidosis, chronic progressive conditions linked to abnormal deposition of normal or abnormal proteins, because these proteins are misshapen and cannot be properly degraded and eliminated by the cell metabolism.
Signs and symptoms
Wild-type transthyretin amyloid accumulates mainly in the
sick sinus syndrome, with ensuing fatigue and dizziness. Wild-type transthyretin deposition is also a common cause of carpal tunnel syndrome in elderly men, which may cause pain, tingling and loss of sensation in the hands. Some patients may develop carpal tunnel syndrome as an initial symptom of wild-type transthyretin amyloid.[2]
There appears to be an increased risk of developing hematuria or blood in the urine due to urological lesions.
Natural course
The disorder typically affects the heart and its prevalence increases in older age groups. Men are affected much more frequently than women,[3] and up to 25% of men over the age of 80 may have evidence of WTTA.[4]
Patients often present with increased thickness of the wall of the main heart chamber, the
ECG signals such as QRS complexes are widely considered a marker of cardiac amyloidosis.[5]
A much better survival has been reported for patients with WTTA as opposed to cardiac AL amyloidosis.[6]
Diagnosis
The condition is suspected in an elderly person, especially male, presenting with symptoms of heart failure such as shortness of breath or swollen legs, and or disease of the electrical system of the heart with ensuing slow heart rate, dizziness or fainting spells.
Congo Red that will be positive in this condition, and immunohistochemistry. However, this disease can now non-invasively be diagnosed with the help of Tc-99m pyrophosphate scintigraphy.[8]
Treatment
No drug has been shown to be able to arrest or slow down the process of this condition.
transthyretin-related hereditary amyloidosis. Permanent pacing can be employed in cases of symptomatic slow heart rate (bradycardia). Heart failure medications can be used to treat symptoms of difficulty breathing and congestion.[11]
A 2021 investigational first-in-human study demonstrated that NTLA-2001, a therapeutic agent based on the
CRISPR-Cas9 system, induces targeted knockout of the transthyretin protein.[12]
Orphan drug status for transthyretin (TTR) amyloidosis
Because of preliminary data suggesting the drug may have activity, the U.S. FDA in 2013 granted
familial amyloidosis (ATTR).[13] However, as of 2015[update] tolcapone was not FDA approved for the treatment of this disease.[14]
