Persons at risk for familial amyloid polyneuropathy (FAP) represent the vast majority of those who undergo pre-symptomatic testing for late-onset neurological diseases (LONDs) in Portugal, according to a 20-year study.
The study, “Twenty Years of a Pre-Symptomatic Testing Protocol for Late-Onset Neurological Diseases in Portugal,” appeared in the journal Acta Médica Portuguesa.
The national protocol of genetic counseling and pre-symptomatic testing for LONDs in Portugal started in 1995 and was then extended to FAP caused by the Val30Met variant in the TTR gene — the most common variant associated with the disease — and other disorders with high incidence in the country.
Ten years after initiating this protocol, an analysis showed that factors such as the gender of the affected parent and the length of the family’s contact with the disease influenced the psychological outcome of pre-symptomatic testing.
The procedure includes a pre-test neurological examination, a psychosocial evaluation and a minimum of two genetic counseling sessions, which explore the motivations for testing and the anticipated impact of possible results, among other factors. The protocol also includes a session to reveal results and psychosocial follow-up at three weeks, six months, and one year. Additional genetic counseling, psychological, social service, and psychiatric sessions are possible.
A total of 1,230 persons (56% female) underwent pre-symptomatic testing at the clinic between 1996 and 2015; 1,174 (78.4%) were at risk for FAP. This high proportion of subjects in the FAP group could be attributed to the recent availability of treatments and advocacy among affected families, the researchers said.
“Adherence to pre-symptomatic testing may change in the future since effective therapies are available (or given the fact that people think effective treatments are imminent),” the scientists said.
Of note, 240 withdrew from the protocol before knowing the results, which could be due to perceiving a higher risk than previously assumed and to inaccurate understanding of the disease, the team hypothesized.
The mean age at testing was 30.7 years, significantly lower in people at risk for FAP (28.8 years). This subgroup also had fewer children (34.3%) than the others, namely Huntington’s disease (HD), Machado-Joseph disease (MJD) — also called spinocerebellar ataxia type 3 — and other LONDs.
Most persons at risk for FAP (55.9%) had not attended university. Having family history of the disease on the maternal side was more predominant among persons at risk for FAP (55.8%), MJD (51.0%), and other LONDs (72.4%) than those in the HD subgroup (45.4%).
As for the reasons to undergo pre-symptomatic testing, 41.7% of the 1,215 people with recorded answers said “to relieve uncertainty,” 23.2% “to prepare for disease onset,” 23.2% “family planning,” and 18% “to inform the offspring.”
The data further showed that 32.4% of 902 individuals anticipated emotional instability after finding they are carriers for any of these diseases. Five manifested suicidal ideation; four of them were at risk for FAP. Also, 21.6% of responders anticipated changes in family planning, 23.5% would seek treatment and medical care, and 22.5% said that nothing would change in their lives.
In the case of a non-carrier result, 41.6% of the responders did not expect changes, 37.4% said they would be happy and relieved, and 4.1% would be willing to have more children.
Most individuals (59.7%) first learned about the program from healthcare professionals. Among those at risk for FAP, family and individual search were the main sources of knowledge.
As for test results, 680 individuals (55.3%) were non-carriers and 550 (44.7%) were carriers. Almost half (45.7%) quit their psychosocial follow-up regardless of test result. One year after result disclosure, 220 individuals (17.9%) were still being followed, most of whom (74.1%) were pre-symptomatic carriers.
A significantly higher proportion of subjects who knew about pre-symptomatic testing via healthcare professionals completed the protocol compared to those with no prior medical advice (23% vs. 12.4%).
Among 293 individuals, the vast majority (87.7%) evaluated the protocol positively, for reasons including its multidisciplinary approach, personalized attention, and psychosocial support. Reasons for negative evaluations included the length of time between collection and results, the protocol’s duration, and information perceived as complex.
Also, 96.8% of 339 respondents would recommend the protocol to relatives and other at-risk persons, for reasons such as access to health information, professional follow-up, and the ability to prepare for the future.
“National genetic services would benefit from evidence-based research on the practice of genetic counseling,” the researchers stated.