Abstract Details

Title Diagnosis and Management of a Sibling Pair With Hereditary Transthyretin Amyloidosis Associated With F44S (p.Phe64Ser) Transthyretin Variant: A Case Report

Topic General Neurology

Presentation(s) General Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 070

Objective We report siblings with amyloidosis both carrying a pathogenic heterozygous mutation F44S in the TTR gene that showed a good response to inotersen treatment.

Background Hereditary transthyretin amyloidosis (hATTR or ATTRv [variant]) is a progressively debilitating, clinically heterogeneous, and fatal disease that results from deposition of insoluble amyloid fibrils in various organs and tissues. Depending on the TTR gene mutation patients often experience multisystem dysfunction including cardiomyopathy, polyneuropathy, or a mixed phenotype.

Design/Methods A 31-year-old male (patient 1) presented with a family history of hATTR and progressive dysesthesia at age 27, prompting genetic testing for amyloidosis. Initial symptoms included pain in both legs, bilateral handgrip and lower limb weakness, vitreous opacifications, erectile dysfunction, gastrointestinal symptoms and bilateral carpal tunnel syndrome (CTS). His 34-year-old brother (patient 2) experienced symptoms of progressive dysesthesia, vitreous opacifications, bilateral CTS and diarrhea at age 31. Genetic testing of patient 2 was prompted after his brother was diagnosed with hATTR. Genetic mutation analysis (2017) identified a heterozygous pathogenic TTR mutation F44S (p.Phe64Ser), and abdominal fat pad biopsy identified amyloid deposits.

Results Since diagnosis of hATTR, the patients have been managed by a multidisciplinary team of physicians including neurologists, geneticists, and cardiologists. Patients were treated with diflusinol (2017) followed by inotersen (2019) for symptoms of polyneuropathy. Patient 1 has reported improvement in his dysesthesia and strength following inotersen treatment. Patient 2 reported feeling “more hopeful” after learning about the availability of different treatment options. Both patients reported absence of disease progression and maintain the ability to complete daily activities without limitations. Moreover, both siblings report no autonomic alterations and resolution of gastrointestinal symptoms.

Conclusions Inotersen treatment slowed disease progression in these patients with F44S TTR mutations, with improvement in selected clinical parameters. Patients with this genotype are likely to benefit from inotersen therapy.

Authors/Disclosures
Eugenie Girouard, MD (CHUM) PRESENTER	Eugénie Girouard has nothing to disclose.
Chadi Darwich, MD (Dr Georges-L- Dumont University Hospital)	Dr. Darwich has nothing to disclose.
John L. Berk	John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca/IONIS. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eidos/BridgBio. John L. Berk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia Therapeutics. John L. Berk has received research support from Alnylam . John L. Berk has received research support from Ionis. John L. Berk has received research support from Eidos/Bridgbio.
	No disclosure on file

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