Combination of Three Tests Can Spot TTR-FAP Early, Study Reports

Cold and pinprick sensitivity in the hands and electrical impulse speed in nerves can help doctors make an early diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP), a study reports.

The research, “Transthyretin familial amyloid polyneuropathy (TTR-FAP): Parameters for early diagnosis,” appeared in the journal Brain & Behavior.

Transthyretin amyloidosis stems from protein clumps called amyloid fibrils occurring in various organs and tissue, causing their dysfunction. The disease affects the peripheral nerves in particular, leading to a condition called polyneuropathy.

The main treatments for TTR-FAP are liver transplants and amyloid-stabilizing agents, which are effective early in the disorder.

Unfortunately, TTR-FAP is a rare disease with non-specific symptoms. This means it is commonly misdiagnosed, often for years. Late treatment reduces the chance of a good outcome.

The danger of late treatment underscores the need for a simple test, or combination of tests, that can signal a patient may have TTR-FAP. Such a signal can prompt doctors to order genetic tests or biopsies to confirm the disease.

A team of researchers decided to take a close look at TTR-FAP’s manifestations to come up with a test for it. The study covered 24 patients with TTR-FAP and 48 with diabetic polyneuropathy (dPNP).

Researchers first determined patients’ neurological impairment score (NIS) and neurological disability score (NDS). The combination of the two allows doctors to make an accurate neurological assessment.

A key finding was that TTR-FAP patients had higher NDS and NIS scores than dPNP patients.

TTR-FAP patients also had less ability to detect cold, to discriminate between cold and warm, and to feel pain when pricked with a pin.

Other tests that researchers looked at were sympathetic skin response (SSR), heart rate variability (HRV), and nerve conduction (NCV).

TTR-FAP patients had more SSR impairment in their upper limbs than dpNP patients, the team discovered. The same was true with HRV and with electrical-impulse-speed scores in the ulnar and sural nerves, which are connected to the hand.

Statistical analysis showed that a combination of ulnar nerve sensory NCV, cold detection, and the pinprick test could differentiate TTR-FAP from dPNP in 82% of cases. In addition, the combination of the three tests was able to differentiate TTR-FAP from chemotherapy-triggered polyneuropathy in 86.7% of cases and from chronic inflammatory demyelinating neuropathy in 68% of cases.

The results prompted the team to conclude that “cold and pinprick sensitivity at the hands and the ulnar sensory NCV seem to be useful for the early detection of TTR-FAP. Of note, these parameters are part of the standard work-up of polyneuropathies (NCV) or can be easily implemented in the routine work-up as ‘bed-side-tests.'”