To study demographics, clinical symptoms, diagnosis dilemma and treatment outcome in patients with hereditary transthyretin-mediated (hATTR) polyneuropathy (PN).

Retrospective chart review of 18 patients with TTR variants mutation, who were evaluated at our clinic (2018-2023).

12/ 18 patients with hATTR variants were diagnosed with hATTR PN.  5/12 patients with neuropathy had V30M mutation. V122I was detected in 4/12 patients. 6/12 had mixed phenotype of cardiomyopathy and polyneuropathy. The median age of onset of symptoms was 69.5 years. (54- 78) Mean diagnosis delays were 37.2 months. (2- 72 months)  90% of patients had autonomic symptoms. Rapidly progressive sensory motor polyneuropathy was identified in 4 patients with a mean diagnosis delay of 30 months. 2 were initially diagnosed as chronic inflammatory demyelinating polyneuropathy. EMG/NCS fulfilled EFNS/PNS criteria for definite demyelinating polyneuropathy in one patient with Ala97Ser.  Multifocal stepwise progression resembling mononeuritis multiplex was seen in one patient with L78H mutation. 83 % of patients received at least one gene silencing therapy.  PN disability score (PND) was stable in most patients on mean follow up of 34.8 months. 5/6 patients treated with inotersen discontinued the medication, due to side effects in 3 patients. 7/8 patients treated with patisiran eventually switched to vutrisiran for convenient dosing. 3/12 patients received tafamidis and gene therapy.

Despite emerging disease modifying treatments, delayed and misdiagnosis are still common. In our cohort, patients who started gene silencing therapy at the earlier stages of the disease had better outcome. Most of our patients (9/12) are on siRNA due to better tolerability.