Abstract
Hereditary transthyretin amyloidosis (ATTRv) is a progressive, life-threatening disease caused by mutations in the TTR gene. It is characterized by marked clinical heterogeneity, and diagnosis is often delayed. Here, we report the tortuous diagnostic process in a patient with late-onset ATTRv carrying a c.349G > T (p.Ala117Ser) mutation in the TTR gene. A 59-year-old man initially presented with distal numbness and weakness in both lower limbs, followed by hoarseness and cough. Over two years, he consulted multiple specialists for these predominant symptoms, but no definitive diagnosis was made. Electrocardiography revealed low limb lead voltages. Echocardiography showed increased echogenicity in the left ventricular posterolateral wall with wall thickness at the upper normal limit. With a strong clinical suspicion of transthyretin amyloidosis, 99mTc-pyrophosphate (PYP) scintigraphy demonstrated cardiac amyloid deposition, and the diagnosis was ultimately confirmed by genetic testing, which identified a heterozygous Ala117Ser mutation in the TTR gene. This case illustrates that in middle-aged and older patients with progressive peripheral neuropathy of unclear cause, atypical symptoms such as hoarseness and cough may serve as important clues to ATTRv. Prompt integration of cardiac imaging and genetic screening can help avoid diagnostic delay.