New Screening Tool for Hereditary Transthyretin Amyloidosis

According to a recent article, researchers have created a new screening tool that will aid in discovering if patients with chronic idiopathic axonal polyneuropathy have the TRR mutation.

Hereditary Transthyretin Amyloidosis (ATTR)

Hereditary ATTR amyloidosis is a familial subtype of amyloidosis. It is an inherited genetic disease affecting the nervous system and the heart.

The genetic mutation that causes hereditary ATTR amyloidosis produces a protein that forms into an abnormal shape. These abnormal, “misfolded” proteins can be deposited and cluster in the body’s nerves and organs, causing complications.

There are three categories of ATTR amyloidosis:

  1. Familial amyloid cardiomyopathy (FAC)
  2. Familial amyloid polyneuropathy (FAP)
  3. Senile systemic amyloidosis, also knows as wild-type ATTR amyloidosis (wtATTR)

Symptoms:

For each patient, the symptoms will depend on which organs are affected by the protein deposits:

Heart

  • Nausea
  • Weight loss
  • Insomnia
  • Progressive fatigue
  • Dizziness
  • Shortness of breath
  • Leg swelling
  • Palpitations and abnormal heart rhythms (atrial fibrillation)
  • Chest pains

Nervous System

  • Peripheral neuropathy
  • Sensorimotor impairment
  • Autonomic neuropathy

Digestive System

  • Nausea
  • Diarrhea or constipation
  • Bladder control issues
  • Weight loss
  • Loss of appetite or a feeling of fullness after eating small amounts

Kidneys

  • Nephrotic syndrome (excess protein in the urine)
  • Swelling of legs, belly, arms, and lungs
  • Renal

Cause:

Amyloidosis is caused by abnormal deposition and accumulation of proteins in the tissues of the body.

In ATTR amyloidosis, a protein called transthyretin (TTR) is the amyloid protein that forms the amyloid deposits, due to a genetic mutation in the TTR gene. 

Diagnosis:

The main diagnostic testing for any amyloidosis disease includes:

  • Blood tests
  • Urine tests
  • Biopsies

After amyloidosis is confirmed, and it is determined that there is transthyretin amyloid protein present, the protein needs to be identified by protein sequence analysis and DNA sequencing to confirm the hereditary ATTR amyloidosis diagnosis.

Chronic Idiopathic Axonal Polyneuropathy (CIAP)

Chronic idiopathic axonal polyneuropathy (CIAP) is a term describing neuropathies with both sensory and motor involvement in a length dependant distribution where neurophysiology reveals axonal damage, neuropathy onset is insidious and shows slow or no progression of the disease over at least 6 months with no aetiology being identified despite appropriate investigations.

Creating the Tool

Researchers evaluated thirty-five patients with hereditary transthyretin amyloidosis (ATTRv), and fifty-five patients with chronic idiopathic axonal polyneuropathy (CIAP). At their initial evaluation, the patient’s clinical and electrophysiological findings were taken. The findings from the two groups were then used to create a compound score, and an ROC (receiver operating characteristic) analysis was done to figure out the best cut-off to differentiate between the two groups.

Results of the Analysis

The results of the evaluations showed that patients diagnosed with ATTRv were diagnosed at a later age, more frequently demonstrated muscle weakness, and had a history of carpal tunnel syndrome. However, these patients also had results from the electrophysiological analysis that showed they had lower compound muscular action potential (CMAP) and sensory action potential (SAP) amplitudes in their nerves. Therefore, researchers created a compound score made up of 7 items that ranged from 0 to 12. The cut-off for the ROC analysis was determined to be less than or equal to 5 points to discriminated ATTRv patients who have a sensitivity of 96.6% and a specificity of 63.6%.

Importance

Researchers were able to discover that there are some clinical and electrophysiological features in patients with CIAP that can help doctors determine if that patient should have a TTR genetic analysis. Therefore, they were able to create a screening tool that is able to be used in a quick and easy manner to help with the screening process of patients.

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