Amyloid myopathy: expanding the clinical spectrum of transthyretin amyloidosis-case report and literature review

Abstract

We identified two patients with transthyretin (ATTR) amyloid myopathy (one ATTR variant amyloidosis, ATTRv; one wild-type ATTR amyloidosis, ATTRwt). Myopathy was the initial manifestation in ATTRwt, whereas it followed neuropathy and cardiomyopathy in ATTRv. The ATTRwt patient showed muscular tracer uptake on ^99mTc-DPD planar scintigraphy at the time of initial diagnosis, consistent with ATTR amyloid myopathy. The ATTRv patient underwent heart transplantation because of progressive heart failure. Within the next two years, progressive myopathic symptoms and extracardiac tracer uptake on ^99mTc-DPD planar scintigraphy were documented, attributable to ATTR amyloid myopathy. Interstitial amyloid deposits were confirmed by muscle biopsy in both patients, with a particularly high amyloid burden in the adipose tissue. This case report highlights the frequent concomitant presence of cardiac ATTR amyloidosis and ATTR amyloid myopathy. ATTR amyloid myopathy may precede cardiac manifestation in ATTRwt or occur after heart transplantation in ATTRv. Due to the high diagnostic accuracy of ^99mTc-DPD scintigraphy for detecting ATTR amyloid myopathy and the emergence of novel therapeutics, it is important to increase the awareness of its presence.

Keywords: 99mTc-DPD scintigraphy; ATTR; ATTR amyloid myopathy; cardiac ATTR amyloidosis; myopathy; neuromyopathy; transthyretin.

Figure 1

^99mTc-DPD whole-body planar imaging (A, C, E, G) and SPECT/CT analysis (B, D, F, H). A and B Patient 1 (ATTRv, before heart transplantation) with Grade 3 cardiac tracer uptake and moderate muscular tracer uptake both on thoracic and abdominal wall (arrow). C and D Patient 1 (ATTRv, 19 months after heart transplantation) without cardiac tracer uptake but significant muscular tracer uptake (gluteal and shoulder regions; histologically confirmed as ATTR amyloid myopathy) (arrow). E and F Patient 1 (ATTRv, 40 months after heart transplantation) without cardiac tracer uptake but visually increasing muscular tracer uptake in gluteal and shoulder regions (arrow). G and H Patient 2 (ATTRwt) with Grade 3 cardiac tracer uptake and extracardiac tracer uptake (thoracic regions and gluteal muscle; histologically confirmed as ATTR amyloid myopathy) (arrow)

Figure 2

Histopathological sections of ATTR amyloid myopathy. ATTRwt, patient 2 A Hematoxylin & Eosin stained cross-section shows atrophic vacuolated fibers with amorphous sarcoplasmic deposits suspicious of amyloid (arrow). B and C Amyloid deposits are clearly identified in bright and polarized light on Congo red stained sections. D Anti-transthyretin immunostaining. ATTRv, patient 1 E Hematoxylin & Eosin stained tissue section shows amyloid deposits in the adipose tissue. F Congo red stained tissue section viewed in polarized light showing characteristic green birefringence. G Anti-transthyretin immunostaining