J Yeungnam Med Sci.  2023 Nov;40(Suppl):S98-S104. 10.12701/jyms.2023.00241.

A rare pathogenic variant identified in a heart transplant recipient with hereditary transthyretin amyloidosis: a case report

• Kim MS
• Lee SY
• Kim KH

• KMID: 2548349
• DOI: http://doi.org/10.12701/jyms.2023.00241

Abstract

Hereditary transthyretin (ATTRv) amyloidosis is a rare and complex genetic disorder that can lead to life-threatening cardiac amyloidosis and rapid disease progression. Early diagnosis and treatment with disease-modifying drugs can improve patient outcomes; however, heart transplantation may be necessary in some patients. We present the unique case of a 65-year-old Korean woman diagnosed with ATTRv amyloidosis after experiencing progressive neurological symptoms, followed by heart failure. Despite the absence of significant symptoms of heart failure, subsequent screening revealed cardiac amyloid infiltration, which caused left ventricular hypertrophy and rapid disease progression. The patient underwent successful heart transplantation, and subsequent genetic testing revealed a pathogenic variant, NM_000371.3:c.425T>C (p.Val142Ala), which affects both the nerves and heart and has not been previously reported in Korea. Our report underscores the potential benefits of heart transplantation in managing advanced ATTRv amyloidosis and emphasizes the need for continued research on the genetic heterogeneity of the disease. Clinicians should consider ATTRv amyloidosis in the differential diagnosis of patients presenting with neurological symptoms and heart failure, particularly in those with a family history of the disease.

Keyword

Amyloidosis; p.Val142Ala variant; Transthyretin

Figure

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  Fig. 1. (A) Initial chest X-ray shows cardiomegaly. (B) Transthoracic echocardiography (TTE) images. Parasternal long axis view. The images show concentric hypertrophy of the left ventricular wall and a small amount of pericardial effusion. (C) Apical four-chamber view of TTE. (D) Global longitudinal strain (GLS) shows reduced longitudinal strain with apical sparing pattern. (E, F) Mitral inflow and mitral annular velocity show grade III diastolic dysfunction. (G) Initial electrocardiography. DT, deceleration time.

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  Fig. 2. Results of the nerve conduction study of the patient. The sensory nerve study demonstrates increased nerve latency and decreased amplitude and peak velocity of the median, sural, and superficial peroneal nerves. The motor nerve study demonstrates decreased amplitude in both peroneal nerves. ADM, abductor digiti minimi; AH, abductor hallucis; Amp, amplitude; APB, abductor pollicis brevis; EDB, extensor digitorum brevis; L, left; Lat, latency; MNC, motor nerve conduction; R, right; SNC, sensory nerve conduction; Vel, velocity; Rec, recommendation; PP, peak to peak; Dur, duration.

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  Fig. 3. Technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. Intense cardiac uptake (arrow) of the radiotracer is observed in both ventricles. (A) Axial view and (B) anterior view. DPD, 3-diphosphono-1,2-propanodicarboxylic acid.

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  Fig. 4. Microscopic findings of endomyocardial biopsy. (A) The specimen shows positivity for transthyretin (immunohistochemical stain for transthyretin). (B) The Congo Red stain shows pink-red deposits of amyloid (Congo Red stain).

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  Fig. 5. Integrated genomics viewer snapshot of the transthyretin variant (NM_000371.3:c.425T>C) identified in the patient (arrow). TTR, transthyretin.

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  Fig. 6. Patient pedigree. The squares and circles represent males and females, respectively, and X marks indicate deceased family members. Blue represents possession of the character under study and black represents an absence. ATTR, amyloid transthyretin; LPV, likely pathogenic variant; TTR, transthyretin.

Reference

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