Tiny tissue samples find early nerve damage, may help in FAP diagnosis
Study shows skin biopsy leads to quicker start to treatment for patients
Using a small sample of tissue from skin — obtained via a skin biopsy — can help diagnose familial amyloid polyneuropathy (FAP) early by looking for the presence of disease-causing toxic amyloid deposits and measuring the number of small nerve fibers in the outermost layer of a person’s skin.
That’s according to a study involving 73 people with hereditary transthyretin amyloidosis (ATTRv) — a group of conditions that includes FAP — and early signs of nerve damage. The researchers were able to diagnose FAP even when standard nerve conduction studies, which measure electrical signals in the nerves, came back as normal.
Based on skin-related findings, one-third of patients were started on gene silencers, a class of FAP-approved treatments that include Onpattro (patisiran) and Amvuttra (vutrisiran).
Skin biopsy “allowed a substantial number of patients to commence gene silencing treatment,” the researchers noted, even when more than three-quarters of the study’s participants had normal or near-normal results on standard nerve tests.
Their study, “Skin Biopsy as a Diagnostic Tool for ATTRv Amyloid Neuropathy in the UK,” was published as a research report in the Journal of the Peripheral Nervous System.
ATTRv comprises a group of conditions marked by the buildup of toxic clumps of the transthyretin protein — known as amyloid deposits — in tissues, causing damage. All forms of ATTRv are caused by mutations in the TTR gene.
In people with FAP, those amyloid deposits damage the peripheral nerves, which branch out from the spinal cord, causing neurological symptoms. When these clumps accumulate in the heart, they can cause heart damage, or cardiomyopathy.
Looking for the presence of amyloid deposits in a skin biopsy — which involves collecting a sample of a person’s skin and surrounding tissue — can help confirm an FAP diagnosis early on, when treatments are likely to be more effective at slowing the disease or preventing complications.
Skin biopsy led to early diagnosis despite normal nerve test results
In this study, a team of researchers at University College London in England focused on 73 ATTRv patients who had early signs of nerve damage. Each underwent skin biopsy at a single hospital in London between July 2021 and October 2023.
Samples of each skin biopsy were tested for the presence of amyloid deposits and intraepidermal nerve fiber density, or the number of nerve fibers within the epidermis, which is the skin’s outermost layer.
The mean age of the participants was 59. Among them, the most common disease-causing mutations were Thr60Ala, seen in 30%, Val122Ile, found for 23%, and Val30Met, seen for 22%. Val30Met is the most common FAP-causing mutation. One person had been previously diagnosed with FAP.
The symptoms suggesting peripheral nerve damage most commonly were abnormal sensations, numbness and muscle weakness in the feet, pain related to nerve damage, and the loss of certain reflexes.
Interestingly, the researchers noted, 78% of the participants had normal or borderline results on standard nerve conduction tests, which measure the speed and strength of electrical signals as they travel along the nerves.
Skin biopsy is a useful and minimally invasive method for detecting [disease-causing] amyloid deposits. … [Its use] has allowed a significant proportion of our patients to access gene silencing therapy early.
The skin biopsy results showed that one-third of all participants had amyloid deposits. Among the 67 with available data, 40% had low intraepidermal nerve fiber density. Samples from 11 participants, or 16% in all, had both signs.
Based on these results, 24 patients (33%) were able to start gene silencing treatment. Slightly more than half of them (54%) had minimal symptoms and/or signs of nerve damage, and three-quarters had already been diagnosed with cardiomyopathy.
These findings led the researchers to conclude that “skin biopsy is a useful and minimally invasive method for detecting amyloid deposits and early small fiber loss.” Moreover, the team noted that its use “has allowed a significant proportion of our patients to access gene silencing therapy early.
The researchers noted that “the majority of [these patients] had cardiomyopathy,” and added that “early diagnosis of ATTRv [with peripheral nerve damage] is critical for treatment decisions.”
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