What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloidosis in the Elderly
• Senile Amyloidosis
• Wild-Type ATTR Amyloidosis

What is Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins)
• These protein aggregates are abnormally-formed and arranged into fibrils (slender fibers). An amyloid build-up can occur locally in only one organ or may occur throughout the body. The organs involved commonly include the skin, heart, liver, spleen, GI tract, kidney, and the nervous system
• When the amyloid build-up occurs in the elderly, without any mutation in the TTR gene, which is responsible for most cases of inherited amyloidosis, it is known as Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis. It is one of the five major subtypes of amyloidosis
• Wild-Type ATTR Amyloidosis can affect both genders, although it is reported almost exclusively in men; symptom manifestation begins during the early 60s
• The TTR gene codes for the transthyretin protein. This protein, although normal, undergoes misfolding in the elderly and forms amyloid particles. The amyloid proteins get deposited throughout the body, primarily in the bones and heart. This may cause symptoms such as carpal tunnel syndrome and abnormal heart rhythms
• Compared to other types of amyloidosis, Wild-Type ATTR Amyloidosis progresses slowly. However, the condition may be fatal, owing to complications such as restrictive cardiomyopathy and heart failure

Who gets Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis? (Age and Sex Distribution)

• Wild-Type Amyloid Transthyretin Amyloidosis occurs in older people, typically beginning in early seventh decade
• This condition occurs almost exclusively in men
• Wild-Type ATTR Amyloidosis is reported worldwide. The exact prevalence of this condition is not known. It can occur in individuals of all backgrounds

What are the Risk Factors for Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis? (Predisposing Factors)

The following are some known risk factors for Wild-Type Amyloid Transthyretin Amyloidosis:

• Age over 60
• Male gender

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis? (Etiology)

• Wild-Type Amyloid Transthyretin Amyloidosis is caused by misfolding of normal transthyretin protein molecules. This protein is coded by the TTR gene
• The misfolding causes the proteins to form amyloid aggregates and subsequently fibrils, which circulate in the bloodstream and get deposited in different tissues
• Wild-Type ATTR Amyloidosis mostly develops in elderly men. The amyloid protein mostly gets deposited in the heart and bones causing symptoms

What are the Signs and Symptoms of Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis?

The signs and symptoms of Wild-Type Amyloid Transthyretin Amyloidosis may depend on the amount of amyloid deposited in the heart and bones. Some individuals with low amounts of deposits may not exhibit any symptoms.

The common signs and symptoms of Wild-Type ATTR Amyloidosis may include:

General signs and symptoms:

• Fatigue
• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Joint pain
• Tingling sensation
• Nausea
• Dizziness
• Anemia

Signs and symptoms related to the heart:

• Shortness of breath
• Irregular heartbeats
• Chest pain
• Enlargement of heart; fluid build-up around the heart
• Excess cholesterol in blood

Signs and symptoms related to carpal tunnel syndrome (where the wrists are affected):

• Numbness 
• Tingling
• Muscle weakness in hands and fingers

In rare cases, the following may also be present:

Signs and symptoms related to spinal stenosis (pressure on the spine):

• Back pain and/or neck pain
• Numbness
• Problems with control of bladder and bowel movement

Signs and symptoms related to peripheral neuropathy (affects hands and feet):

• Pain 
• Numbness
• Tingling sensation or “pins and needles” sensation 
• Weakness

How is Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis Diagnosed?

A diagnosis of Wild-Type Amyloid Transthyretin Amyloidosis is based on the following tests and exams:

• A thorough physical examination
• Evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms; specifically, for a combination of carpal tunnel syndrome and heart problems
• Blood tests:
  • To check heart function (cardiac biomarkers for stress on the heart)
  • To measure amyloid proteins
• Electrocardiography and echocardiography for checking heart function
• Imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Tissue biopsy: A biopsy of an affected organ or tissue is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In Wild Type ATTR Amyloidosis,
  • Biopsy of tissue from the affected organ or tissue may be necessary
  • Amyloid deposit from affected tissue is detected using a staining procedure. When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis?

The potential complications of Wild-Type Amyloid Transthyretin Amyloidosis include:

• Stiffness and pain in joints leading to difficulty with movement
• Dizziness and risk of fall, if one stands up too quickly from a seated position
• Progression of heart problems to restrictive cardiomyopathy, which may lead to:
  • Arrhythmias: Abnormal heart rhythm, which can be triggered by physical exertion
  • Sudden cardiac arrest 
  • Embolism: Development of blood clots in the heart which may get into the bloodstream and obstruct blood supply to many important organs
  • Edema: Fluid buildup in the lungs, abdomen, legs, and feet, due to ineffective heart pumping
  • Stroke

How is Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis Treated?

Currently, there are no treatment options available to cure Wild-Type Amyloid Transthyretin Amyloidosis. However, there are treatment measures available to ease the symptoms of the disease and slow its progression.

The treatments are unique to the individual and depend on the organs affected. These options include:

• Restricting fluids (to limit fluid accumulation in the body)
• Diet: Having frequent and small meals through the day, with reduced fat and sodium content
• Moderate exercise
• Diuretics to get rid of excess salt and water from the body
• Medication for pain, which may include gabapentin and pregabalin
• Medications for restoring normal heart function:
  • Beta blockers
  • Angiotensin converting enzyme (ACE) inhibitors 
  • Angiotensin receptor blockers 
  • Calcium channel blockers
  • Digoxin
• Pacemaker implantation to improve heart function
• Heart transplantation for severe dysfunction of heart
• Surgery to repair carpal tunnel syndrome

How can Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines available to prevent Wild-Type Amyloid Transthyretin Amyloidosis
• Individuals over the age of 60 years and affected by carpal tunnel syndrome as well as with heart problems, should get checked for Wild-Type ATTR Amyloidosis. This may help in identifying the condition early and delaying its progression
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as amyloidosis

Regular medical screening at periodic intervals with tests, and physical examinations are highly recommended.

What is the Prognosis of Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis? (Outcomes/Resolutions)

• The prognosis of Wild-Type Amyloid Transthyretin Amyloidosis is determined by the severity of symptoms and overall health of the affected individual
• If the amyloid deposits in the heart lead to restrictive cardiomyopathy, it may cause heart attack, stroke, or embolism, which may be even fatal

Additional and Relevant Useful Information for Wild-Type Amyloid Transthyretin (ATTR) Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum