Do not stop at the variant: a reversible cause of small-fiber neuropathy symptoms in an ATTRv carrier

Presymptomatic genetic testing in relatives of hereditary transthyretin amyloidosis (ATTRv) index cases enables early carrier identification and timely treatment, but a confirmed pathogenic variant carries the risk of premature diagnostic closure when new symptoms arise.

A 25-year-old asymptomatic carrier of TTR: p.Val142Ile, whose father had neurological-predominant ATTRv, developed lower limb heaviness, burning pain, hyperesthesia, dysautonomia, and gastrointestinal symptoms. Cardiac work-up was unremarkable; electrochemical skin conductance testing was abnormal and gastric solid emptying scintigraphy was borderline. Before pursuing skin biopsy, a broad differential was investigated, revealing profoundly suppressed thyroid-stimulating hormone (TSH), elevated total triiodothyronine (T3), positive anti-thyroid peroxidase antibody (anti-TPO) and positive TSH receptor antibody (TRAb), confirming Graves' disease. Antithyroid treatment led to normalization of thyroid function and improvement of symptoms.

Autoimmune thyroid disease may be an underrecognized, reversible cause of neuropathic symptoms. Systematic differential diagnosis is essential before attributing new symptoms to amyloidosis, preventing unnecessary initiation of disease-modifying therapy in patients with treatable alternative etiologies.