A case of cardiac amyloidosis in an elderly Japanese patient with amyloidogenic transthyretin Val122Ile variant

Abstract

A 76-year-old Japanese man with a history of stomach cancer and chronic atrial fibrillation was referred to our department with left atrial thrombus. He had a history of gastric amyloidosis diagnosed by a pathological specimen of the stomach; however, further examination for amyloidosis was not performed. The patient displayed clinical signs and symptoms of heart failure and echocardiography showed a thick left ventricular wall. Since cardiac amyloidosis was suspected, the patient underwent cardiac magnetic resonance imaging and ^99mTc-pyrophosphate scintigraphy. These results are consistent with transthyretin amyloidosis (ATTR amyloidosis). DNA analysis of transthyretin (TTR) was performed and a heterozygous Val122Ile mutation was identified. Notably, his only son requested the analysis; however, no mutations were noted. ATTR Val122Ile is one of the mutations in TTR that are associated with hereditary amyloidosis, causing severe cardiomyopathy. The prevalence of the ATTR Val122Ile mutation is 3.9% in the African-American population. However, the occurrence of this mutation in Asian populations is very rare. This is the second reported case of the ATTR Val122Ile variant in Japan and the first case tested including familial genes. <Learning objective: Transthyretin amyloidosis (ATTR) Val122Ile variant is rare in Asian people. This is the second case of ATTR Val122Ile variant in Japan and the first case tested including familial genes. This case suggests this mutation is present even in Asian people. It is important to evaluate transthyretin gene mutations even in elderly ATTR cardiac amyloid without apparent family history of amyloidosis. If there is a gene mutation, it is necessary to search for transthyretin mutation within the family members.>.

Keywords: Amyloid; Heart failure; Transthyretin; Transthyretin amyloidosis; Val122Ile.

Fig. 1

(A) The chest radiograph taken upon admission. (B) The chest-abdominal contrast-enhanced computed tomography on admission. An arrow points to the left atrial thrombus. (C) The electrocardiogram on admission. (D) Transthoracic echocardiography showing left ventricular hypertrophy. (E) Transesophageal echocardiography revealed left atrial thrombus.

Fig. 2

(A, B) Cardiac magnetic resonance imaging showed diffuse sub-endocardial heterogeneous increased signal on delayed contrast-enhanced inversion recovery T1-weighted images. (C, D) ^99mTc-pyrophosphate scintigraphy showed increased isotope uptake in the left ventricle. (E) Congo red stained biopsy of stomach showed amyloid deposits on lamina muscularis mucosae (x40 magnification). (F) Hematoxylin and eosin stain (x100 magnification). (G) On immunohistochemistry, staining was positive for anti- transthyretin antiserum (x100 magnification).

Fig. 3

(A) Substitution of Ile for Val at position 122 in TTR exon was noted in the DNA sequence analysis of transthyretin (TTR) in the patient. (B) The mass spectrometry showed normal TTR of the patient’s son. (C) The family tree of the patient. ATTR, transthyretin amyloidosis.