• Katsuya Nakamura, Tsuneaki Yoshinaga, Akiko Sakyu, Akira Matsushima, Yuka Yonehara, Tomomi Kojima, Masumi Ishikawa, Emiko Kise, Tomoki Kosho, and Yoshiki Sekijima.
• Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
• Amyloid. 2024 Sep 1; 31 (3): 179183179-183.

BackgroundHereditary transthyretin-related amyloidosis is an autosomal dominant disorder. Recently, disease-modifying therapies (DMTs) have been developed. For at-risk individuals, genetic analysis aids in the early administration of medical care; however, few studies have evaluated the current status of genetic counselling and management of presymptomatic carriers of amyloidogenic variants.MethodsWe retrospectively evaluated the medical records of 202 consecutive participants.ResultsA total of 103 clients who received genetic counselling for predictive testing were at-risk, and 83 underwent predictive testing. Genetic testing results were positive in 33 patients, 11 of whom had confirmed amyloid deposition and were administered DMTs. For presymptomatic V30M (p.V50M) carriers, 32.0 ± 2.4 years (median ± standard error) was the age when amyloid deposition was first identified (95% confidence interval 27.4-36.6). Serum transthyretin (TTR) levels decreased serially with an estimated slope of -1.2 mg/dL/year.ConclusionsOur study suggests the clinical utility of management using a combination of predictive testing and monitoring methods. Psychosocial support should be considered with collaboration between geneticists/genetic counsellors and psychologists. For a more optimised protocol for monitoring and designing future interventional trials in presymptomatic carriers, prospective cohort studies are necessary to clarify the natural history, particularly in the early stages of the disease.

22 keywords...

hide…