Genetic sequencing can help to diagnose familial amyloid polyneruopathy (FAP) in people diagnosed with neuropathy of unknown origin — and sequencing is more reliable than biopsies for diagnosis, the results of a recent study suggest.
The study, titled “Prevalence of hereditary transthyretin amyloid polyneuropathy in idiopathic progressive neuropathy in conurban areas,” was published in the journal Neurological Research and Practice.
As more treatment options for FAP become available, it is important to be able to diagnose the condition, particularly in patient populations in which the rare, inherited, progressive disease is less common. While FAP affects as many as 1 in 1,000 people in certain areas of Portugal and Sweden, it is usually much rarer.
Here, researchers performed genetic testing at a clinic in Germany on 102 people who had been diagnosed with an “idiopathic” neuropathy — that is, a nerve disease for which the root cause is not clear. For all participants, the TTR gene, which is mutated in FAP, was sequenced in its entirety.
The vast majority of participants had wild-type (normal) TTR sequences. Two of the participants, though, tested positive for FAP-causing mutations: a 71-year-old male originally from Kazakhstan, and a 62-year-old female of Polish origin.
Interestingly, the female patient had a mutation that is known to cause FAP but, prior to this study, had only been reported in people of Japanese ancestry.
Additionally, in both of these individuals, previous biopsies had returned results that were not suggestive of FAP.
“As a consequence,” the researchers said, “the importance of molecular genetic analysis to diagnose transthyretin amyloidosis [FAP] and its superiority over biopsy cannot be overemphasised.”
Both newly diagnosed individuals promptly began appropriate treatment, for example, with Vyndaqel.
Broadly, the results of this study support the idea that FAP should be considered in cases in which a neuropathy of unknown origin — even if symptoms or previous test results don’t quite match up with what is considered typical in FAP. The study results also highlight genetic testing as the gold standard for diagnosis.
“[FAP] is probably not as rare as it is often thought to be in idiopathic polyneuropathy patients in comparable settings,” the researchers said.
“In conclusion, in conurban areas in non-endemic regions, molecular genetic analysis for [FAP] should be considered in cases of idiopathic polyneuropathy regardless of family history and biopsy results to initiate proper treatment of a potentially life-threatening disease,” they concluded.