Skin plus salivary gland biopsies help to diagnose FAP early: Study
Analyzing both tissues raised group's overall detection rate from 70% to 88%
Examining small samples of tissue from the skin and the salivary glands, those that produce saliva, increases the chances of detecting the toxic protein clumps that cause familial amyloid polyneuropathy (FAP) early in the disease’s course, a study reported.
Its findings suggest that analyzing both these tissues, whose collection comes through minimally invasive biopsies, “may be of major interest to confirm entry in the disease at very early-stage [FAP], with implications in disease-modifying treatment initiation,” the researchers wrote.
The study, “Minimal invasive biopsies are highly sensitive for amyloid detection in hereditary transthyretin amyloidosis with polyneuropathy,” was published as a research report in the Journal of the Peripheral Nervous System.
Amyloid deposits in skin tissue are known to help confirm a FAP diagnosis
Also referred to as hereditary transthyretin amyloid polyneuropathy, FAP is caused by genetic mutations that result in a faulty, misfolded version of the transthyretin protein that’s prone to forming toxic clumps known as amyloid deposits.
These deposits damage organs, affecting their ability to function. In FAP, the peripheral nerves that run outside the brain and the spinal cord are mainly affected, resulting in disease symptoms like numbness and weakness.
The presence of amyloid deposits in a tissue biopsy can help to confirm a FAP diagnosis in early stages, when disease treatments can be more effective at slowing progression and preventing complications. Biopsy samples can be obtained from tissues like the skin, and from the salivary glands of the mouth.
FAP, the scientists noted, “belongs to the 5% of rare diseases” with approved and targeted disease treatments.
Researchers know that obtaining a skin biopsy sample — a simple and lightly invasive procedure — can help to diagnose FAP in people carrying disease-causing genetic mutations but not yet showing symptoms.
Researchers in France and Italy now tested how well a biopsy from the labial glands — the most accessible salivary glands, found just under the inner surface of the lip — works in detecting amyloid deposits. They examined labial gland samples alone and in combination with a punch skin biopsy taken from a patient’s ankle, thigh, or wrist.
Analyzed data covered 171 adults with FAP who underwent labial gland and skin biopsies in the same year, and were seen at a single specialized center in France between January 2012 and December 2023.
Patients were divided into three groups: 49 carried Val30Met — the most common FAP-causing mutation — and had early-onset disease, 58 carried Val30Met but had late-onset disease, and 64 had less common disease-causing genetic mutations.
Significant increase in disease detection seen with dual tissue analysis
The disease had a median duration of two years in this group, and those with an early-onset Val30Met mutation developed symptoms at significantly younger ages (median age, 33) than patients with a late-onset Val30Met (67 years old) or non-Val30Met mutation (64 years old).
Biopsy samples from both the labial salivary glands and skin were tested using Congo red stain, a dye that makes amyloid deposits visible under a microscope.
These clumps were present in the salivary glands of 72% of patients, ranging from 59% in the non-Val30Met group to 94% in the early-onset Val30Met group, results showed. In skin biopsies, the detection rate was 77% for all patients, ranging from 64% in the late-onset Val30Met group to 94% in the early-onset Val30Met group.
While each approach detected amyloid deposits in about 70% of patients, showing comparable performance, combining both approaches significantly increased the detection rate to 88%.
Minimally invasive biopsies ‘highly effective’ at finding FAP at earliest stages
Significantly higher detection rates with this dual approach specifically were seen among patients with late-onset Val30Met mutation (64%-67% vs. 83%) and those with a non-Val30Met mutation (59%-75% vs. 86%).
In patients with an early-onset Val30Met mutation, each type of biopsy resulted in a 94% rate of amyloid deposit detection, while combined biopsies detected the toxic clumps in 96% of patients. However, this difference was not statistically significant.
Findings suggest that analyzing both salivary glands and skin biopsies increases the likelihood of confirming a diagnosis, particularly for patients with late-onset Val30Met mutation or mutations other than Val30Met.
Analysis of both samples, especially in those two patient groups, “increased amyloid detection” at rates “comparable to or even better than those of nerve biopsy,” the researchers wrote.
Both procedures also were “well tolerated with no significant complications reported,” they added, while noting that a biopsy of the labial salivary glands “cannot be repeated over time since there is a risk of small nerve … lesions.”
“To our knowledge, we are the first to demonstrate that combining minimal invasive [labial salivary gland biopsy] and [skin biopsy] is highly effective in detecting amyloid deposits even at the earliest stage of symptomatic disease,” the researchers concluded.
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