Screenings for Fabry Disease, Amyloidosis Provide Little Value in Polyneuropathy Patients, Study Suggests

Screenings for Fabry Disease, Amyloidosis Provide Little Value in Polyneuropathy Patients, Study Suggests

A study in a Nordic population found no apparent clinical benefit in screening patients with idiopathic small fiber neuropathy or mixed neuropathy for hereditary ATTR amyloidosis and Fabry disease, identifying no definite cases of either disorder.

The study, “Screening for Fabry disease and hereditary ATTR amyloidosis in idiopathic small fiber and mixed neuropathy,” was published in Muscle & Nerve.

Polyneurophathy, or peripheral neuropathy, is a global definition for a group of disorders that damage peripheral nerves, causing weakness, numbness, and pain in the hands and feet. It is a relatively common disorder estimated to affect between 1-3% of the general population worldwide and up to 6-7% of the elderly.

However, the specific causes underlying these disorders are still poorly understood, especially in patients affected by slow-progressing disease forms, such as sensory axonal polyneuropathy and small fiber neuropathy (SFN).

Previous screening studies have shown that two genetic disorders — Fabry disease and hereditary ATTR (hATTR) amyloidosis — can lead to the development of painful polyneuropathy that affects small nerve fibers. However, study results have been inconsistent and difficult to interpret.

Now, researchers wanted to determine whether performing genetic screenings for Fabry disease and hereditary ATTR amyloidosis in a group of patients with idiopathic SFN or mixed neuropathy could be beneficial in a clinical setting.

Between October 2015 and February 2017, the retrospective and prospective multicenter study enrolled a total of 155 patients from four different Nordic countries — 31 from Denmark, 39 from Finland, 39 from Norway, and 46 from Sweden — who were diagnosed with idiopathic SFN (64.5%) or mixed neuropathy (35.5%).

Researchers collected blood samples from all patients who were then genetically screened for disease variants of the GLA gene (alpha-galactosidase A) associated with Fabry disease and the TTR gene (transthyretin) linked to hereditary ATTR amyloidosis.

Screening results revealed that one patient carried a possible disease variant of the GLA gene (R118C). However, further analysis failed to confirm a Fabry disease diagnosis due to a lack of typical disease symptoms, including decreased alpha-galactosidase A activity, skin alterations, fat deposits around the eyes, and heart abnormalities.

On the other hand, no disease variants of TTR were found among the study participants.

Since no definite cases of Fabry disease and hereditary ATTR amyloidosis were identified in this group of Nordic patients, the authors believe such genetic screenings do not bring substantial clinical benefits.

“Screening for hATTR amyloidosis and FD [Fabry disease] in patients with idiopathic SFN without any additional disease-specific symptoms or clinical characteristics in a Nordic population thus appears to be of little value in a clinical setting. Nevertheless, the divergent results in earlier genetic screening studies in patients with idiopathic SFN suggest that in some populations screening for these disorders might be worthwhile,” the researchers wrote.

One comment

  1. GLA gene R118C cannot be excluded as not causing fabry disease.
    The mutation has been around for at least 2000 years and was probaly spread by Roman invasion.
    Over such a long time and over diverse populations many of the survivers who carry this mutation will have a modified disease progression, but if they live beyond middle age symptoms will develop and their main cause of death may be heart failure or stroke.

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