hATTR-PN vs. CIDP: Why misdiagnosis happens and how to get the right test
Fact-checked by When diagnosing hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), doctors need to differentiate it from other conditions that cause similar symptoms, including chronic inflammatory demyelinating polyneuropathy (CIDP).
A genetic disease, hATTR-PN damages peripheral nerves, or those found outside the brain and spinal cord, in different parts of the body. CIDP also damages peripheral nerves, but it has an autoimmune origin. Despite their different origins, the diseases can cause similar, nonspecific symptoms of nerve damage.
Diagnostic tests and certain red flag symptoms can help distinguish hATTR-PN from CIDP, which is essential as their treatments also differ.
Why hATTR-PN and CIDP can look similar
While hATTR-PN and CIDP cause nerve damage in different ways, the resulting symptoms are often similar.
In hATTR-PN, mutations in the TTR gene, which encodes the transthyretin (TTR) protein, destabilize the protein and increase its tendency to misfold. Abnormal TTR proteins tend to aggregate into clumps called amyloid deposits, which can damage nerves and disrupt their function. Specifically, in hATTR-PN, toxic amyloid deposits can damage axons — the long, fiber-like projections that transmit signals between nerve cells.
CIDP occurs when the immune system begins attacking myelin — the protective coating surrounding the axons of some nerve cells that helps signals travel more efficiently. Myelin loss, or demyelination, leaves axons unprotected and can lead to permanent nerve damage if not treated.
The symptoms that develop as a result of axon damage or myelin loss often overlap, leading to misdiagnoses.
Symptoms that may overlap
Overlapping symptoms are a major reason why hATTR-PN is mistaken for CIDP in some cases. These may include:
- abnormal sensations, such as numbness or tingling
- muscle weakness and walking difficulties
- dulled reflexes throughout the body
Neuropathic pain, a type of pain related to nerve damage, can also occur in both conditions, but is more commonly a symptom of hATTR-PN.
Clues that may point more strongly to hATTR-PN
Certain symptoms may raise red flags, suggesting a possible CIDP misdiagnosis and pointing toward hATTR-PN instead. These can also arise during the initial stages of diagnosis and may include:
- poor response to immunotherapies for CIDP
- symptoms of autonomic dysfunction, or problems caused by damage to nerves controlling unconscious and involuntary bodily functions
- a family history of hATTR-PN, or of symptoms consistent with hATTR-PN
- more severe neuropathic pain
Diagnostic tests that distinguish hATTR-PN from CIDP
Several types of tests can help distinguish hATTR-PN from CIDP.
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| Test | hATTR-PN results | CIDP results |
|---|---|---|
| Genetic testing | TTR mutations are present | No TTR mutations |
| Blood test | No CIDP-associated antibodies | CIDP-associated antibodies may be present |
| Nerve biopsy | Amyloid deposits, axon damage, possible myelin damage | No amyloid deposits, prominent myelin damage |
| Nerve conduction study | Nerve signal transmission problems more consistent with axon damage | Nerve signal transmission problems more consistent with myelin damage |
If TTR genetic testing shows mutations are present, this is a strong sign that hATTR-PN is more likely than CIDP.
Although myelin damage is a typical feature of CIDP, it can also sometimes occur in hATTR-PN, complicating the interpretation of nerve biopsy and nerve conduction studies. Amyloid deposits don’t necessarily affect myelin directly, but axon damage related to the condition can cause demyelination
Why the right diagnosis matters for treatment
Because hATTR-PN and CIDP have different underlying causes, they require different treatments. Correctly identifying each condition to start appropriate treatment early is crucial in both hATTR-PN and CIDP.
In hATTR-PN, misdiagnosis may delay the start of treatment that could slow or halt disease progression, potentially leading to poorer long-term outcomes. Treatments for hATTR-PN that target the root causes of the disease typically focus on reducing the buildup of amyloid deposits by:
- silencing the TTR gene to reduce TTR production
- stabilizing TTR’s structure to prevent the protein from misfolding and forming clumps
Treatments for CIDP, on the other hand, typically focus on suppressing or modulating the immune system to prevent further myelin damage. If CIDP remains undiagnosed and untreated for a long time, it can lead to permanent nerve damage and disability.
Amyloidosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
