Work

Case Report: Gastrointestinal-onset hereditary transthyretin amyloidosis with cardiomyopathy and equivocal 99mTc-PYP scintigraphy: diagnosis by florbetapir PET-guided skeletal muscle biopsy and genetic testing

Year: 2026

Type: article

Abstract: Background Hereditary transthyretin amyloidosis (ATTRv) is a multisystem disease driven by pathogenic transthyretin (TTR) variants. Gastrointestinal presentations may precede cardiomyopathy, leading to diagnostic delay. Methods and results A 52-year-old man presented with refractory watery diarrhoea, weight loss, orthostatic hypotension, bradycardia, and distal sensory symptoms; electromyography confirmed carpal tunnel syndrome. Cardiac imaging strongly suggested cardiac amyloidosis, while monoclonal protein studies were negative. Rectal biopsy confirmed amyloid. 99m Technetium-pyrophosphate ( 99m Tc-PYP) scintigraphy was equivocal with a Perugini score of 1. Because endomyocardial biopsy was declined, 1 ⁸F-florbetapir positron-emission tomography/computed tomography ( 1 ⁸F-florbetapir PET/CT) demonstrated myocardial and right gluteal muscle uptake, directing a gluteal biopsy that yielded amyloid confirmation. Whole exome sequencing identified a heterozygous TTR c.236C > A (p.Thr79Lys; historically p.Thr59Lys) variant. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of the amyloid-laden tissue identified TTR (88.7% coverage) with two mutant peptides confirming this substitution. Tafamidis 61 mg daily and dapagliflozin 10 mg daily were initiated. After 3 months, diarrhoea, dyspnoea, and fatigue improved; NYHA class improved to II and left-ventricular ejection fraction (LVEF) increased from 36% to 49%, accompanied by a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (from 887 to 408 pg/mL) and high-sensitivity troponin T (hs-TnT) (from 23.9 to 12.1 ng/L). Conclusion Refractory diarrhoea with orthostatic hypotension and carpal tunnel syndrome should raise suspicion for ATTRv. Equivocal bone scintigraphy does not exclude hereditary ATTR cardiomyopathy, and amyloid binding PET can guide safer extracardiac biopsy. Integrating multimodality imaging, histology, and genetics shortens diagnostic delay in this now treatable disease.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2026.1928392