Diagnosis of Amyloidosis

1. Blood and Urine Tests

The first step in diagnosing amyloidosis is to check for abnormal proteins in the blood and urine. Since amyloid proteins are often produced in excess or misfolded, they can sometimes be detected in these tests.
Doctors may perform a Serum Free Light Chain (FLC) test to measure the levels of light chains in the blood. In AL amyloidosis, abnormal plasma cells in the bone marrow produce excessive light chains, which can misfold and form amyloid deposits. High levels of free light chains suggest that AL amyloidosis may be present.
Similarly, a urine protein test can help detect proteinuria, which occurs when amyloid damages the kidneys, causing large amounts of protein to leak into the urine. This is common in AL amyloidosis and AA amyloidosis, both of which frequently affect the kidneys.
Doctors may also measure Serum Amyloid A (SAA) protein levels in the blood, which are elevated in AA amyloidosis (the type associated with chronic inflammation). If doctors suspect heart involvement, they may check for cardiac biomarkers like B-type natriuretic peptide (BNP) and troponin, which indicate heart strain caused by amyloid deposits.

2. Imaging Tests

Since amyloidosis affects multiple organs, imaging tests help doctors assess how much damage has occurred and identify affected organs. Different types of imaging scans are used depending on the suspected organ involvement.
For cardiac amyloidosis, an echocardiogram (heart ultrasound) is often the first imaging test. It helps detect thickened heart walls and abnormal heart movement, which are signs of amyloid deposits in the heart. Cardiac MRI (magnetic resonance imaging) provides even more detailed images, showing whether the heart tissue has been infiltrated by amyloid proteins.
For ATTR amyloidosis (hereditary or wild-type ATTR), a nuclear imaging scan called a PYP scan (pyrophosphate scan) or DPD scan is used. This scan detects calcium deposits in amyloid plaques, making it a highly effective test for distinguishing ATTR amyloidosis from AL amyloidosis. Unlike AL amyloidosis, ATTR amyloidosis does not typically require a biopsy if the PYP scan confirms amyloid deposits in the heart.
If doctors suspect kidney, liver, or spleen involvement, they may use an abdominal ultrasound, CT scan, or MRI to check for enlarged organs or abnormal tissue changes. In some cases, an X-ray may be used to look for bone or joint involvement in dialysis-related amyloidosis (DRA).

3. Biopsy (Confirming Amyloid Deposits)

A biopsy is the most definitive test for amyloidosis because it directly examines tissue samples for amyloid deposits. A small piece of tissue is taken from an affected organ (such as the kidney, liver, or heart) or from abdominal fat, bone marrow, or the gums.
Once the sample is obtained, it is stained with a special dye called Congo Red. Under a polarized light microscope, amyloid deposits appear apple-green, which confirms the presence of amyloidosis. This is considered the gold standard for diagnosis.
If a patient has AL amyloidosis, doctors may also perform a bone marrow biopsy to check for abnormal plasma cells producing the misfolded proteins. If hereditary amyloidosis is suspected, genetic testing is performed to identify TTR gene mutations.

4. Identifying the Type of Amyloidosis

Once amyloidosis is confirmed, the next step is to determine which type of amyloid protein is causing the disease. This is important because different types of amyloidosis require different treatments.
A technique called mass spectrometry is used to analyze biopsy samples at a molecular level. This test can identify the specific type of amyloid protein involved, such as light chains (AL amyloidosis), Serum Amyloid A (AA amyloidosis), or Transthyretin (ATTR amyloidosis).
In hereditary ATTR amyloidosis, genetic testing is used to check for mutations in the transthyretin (TTR) gene. If a person has a family history of amyloidosis, genetic testing helps determine whether they have inherited the condition.
For AL amyloidosis, additional tests such as immunofixation electrophoresis (IFE) are used to detect abnormal light chains in the blood and urine.

5. Functional Tests for Organ Damage

Since amyloidosis affects vital organs, additional tests are needed to measure how much damage has been done and whether treatment is needed immediately.

  • Heart Tests – An electrocardiogram (ECG) checks for abnormal heart rhythms caused by amyloid deposits. A stress test may also be done to evaluate heart function.
  • Kidney Tests – Blood tests measuring creatinine and estimated glomerular filtration rate (eGFR) help determine if kidney function is declining.
  • Liver Function Tests – Blood tests for ALT, AST, and bilirubin assess whether amyloid is affecting the liver.
  • Nerve Tests – If amyloidosis is suspected in the nervous system, a nerve conduction study (NCS) can help identify nerve damage.
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