Nerve damage in hands & feet
Nazila Rad, M.D
Board Certified Neurologist & Clinical Neurophysiologist
3655 Lomita Blvd Ste 302
Torrance, CA 90505
Peripheral Neuropathy associated with Transthyretin amyloidosis
Peripheral neuropathy is nerve damage, usually in the hands and feet. Symptoms of peripheral neuropathy are sensory symptoms such as pins and needles, uncomfortable tingling and burning sensations, oversensitivity, reduced sensation of touch, or sensitivity to pain. It also can manifest as poor balance or muscle weakness.
A common cause of peripheral neuropathy is diabetes, but it can also result from inflammation, infections, and exposure to toxins, autoimmune conditions, genetic causes or it can be idiopathic. Accurate diagnosis is crucial to control and manage the symptoms.
Here we explain a genetic condition that can cause progressive peripheral neuropathy, called Transthyretin amyloidosis.
Transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body’s organs and tissues.
These protein deposits most frequently occur in the peripheral nervous system.
-Protein deposits in these nerves result in a loss of sensation in the extremities (peripheral neuropathy).
-The autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis
-Other areas of amyloidosis include the heart, kidneys, eyes, and gastrointestinal tract. The age at which symptoms begin to develop varies widely among individuals with this condition, and is typically between ages 20 and 70.
There are three major forms of transthyretin amyloidosis, which are distinguished by their symptoms and the body systems they affect.
The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions.
Impairments in bodily functions can include sexual impotence, diarrhea, constipation, problems with urination, and a sharp drop in blood pressure upon standing (orthostatic hypotension).
Some people experience heart and kidney problems as well.
Various eye problems may occur, such as dry eyes, increased pressure in the eyes (glaucoma). Some people with this form of transthyretin amyloidosis develop carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers.
Investigate cause of neuropathy
If the clinical suspicion for hATTR is high, for example, if a patient has a painful, axonal type neuropathy, dominant family history, cardiac and/or autonomic symptoms or an ethnicity with a high prevalence of hATTR, investigations for the cause of the neuropathy may be very limited. hATTR amyloidosis can be excluded if genetic testing confirms wild-type TTR, as sequence analysis of the gene detects more than 99% of pathogenic variants.
In the absence of diabetes, the development of a neuropathy with autonomic involvement should always raise the possibility of amyloidosis. In more ambiguous cases, a broad, routine approach to investigating neuropathies may be taken, especially to exclude acquired causes.
The most common misdiagnosis of amyloidosis affecting the peripheral nerves is CIDP as patients with hATTR can have slowed conduction on neurophysiology and raised CSF protein. In a study of 150 patients with ATTRm, 42 (32%) had been misdiagnosed, 30 (61%) of which were initially diagnosed as CIDP, and 2% as vasculitic neuropathy. Also, as amyloid can have patchy deposition, it can also be misdiagnosed as a radiculopathy or plexopathy. As such there should be a high suspicion for ATTRm in patients diagnosed with CIDP that do not respond to immunomodulatory treatment.
In 2018, two novel treatments for hATTR amyloidosis related neuropathy, patisiran and inotersen attained EMA and United States Food and Drug Administration (FDA) approval following two successful phase-3 trials both published in New England Journal of Medicine in July, 2018. Both drugs are genetic therapies that suppress ATTRwt and ATTRm synthesis in the liver through different but similar mechanisms and represent a paradigm shift in the management of this devastating disease.
Therefore, it is imperative to see neurologist as soon as possible to arrive at accurate diagnosis as may change quality of your life.