Late-Onset Hereditary Transthyretin Amyloidosis Val30Met in an Elderly Person in a Non-Endemic Area

Abstract

Introduction: Patients with late-onset transthyretin Val30Met-associated hereditary transthyretin amyloidosis (hATTR) in non-endemic areas still remain undiagnosed because of diverse clinical presentations and various non-specific symptoms.

Case presentation: A 76-year-old male patient presented with progressive numbness, pain and weakness in his limbs, sweating, constipation and unexplained weight loss over the past seven years. He has shortness of breath, edema and hypotension for one month. The low QRS voltage on limb leads was not consistent with left ventricular hypertrophy, which is an important clue of cardiac amyloidosis (CA). The results of echocardiography speckle tracking imaging were consistent with CA. Serum immunofixation electrophoresis was negative, and serum-free light chain Fκ/Fλ ratio is normal or close to normal (0.26-1.65) for the patient, so AL amyloidosis can be excluded. A missense mutation c. 148 G-A Val30Met (p.Val50Met) was detected in TTR gene sequencing. The genetic finding confirmed hATTR Val30Met, familial amyloid polyneuropathy (FAP) and CA for the patient. The treatment effect was poor, and he died of cardiac involvement.

Conclusion: It is challenge to make early diagnosis in patients with hATTR, due to the diversity of symptoms. Echocardiography is a vital tool in initial diagnosis. Genetic testing played vital roles in the definitive diagnosis of this disease. Raising awareness is critical for early diagnosis and provides opportunities for early treatment.

Keywords: cardiac amyloidosis; familial amyloid polyneuropathy; hereditary transthyretin amyloidosis; speckle tracking imaging.

Figure 1

Chest X-ray indicated bilateral pulmonary inflammation and pleural effusion.

Figure 2

ECG showed sinus rhythm, left deviation of ECG axis, QRS low voltage on leads of limb, abnormal Q wave of II, III and AVF, and QRS presented as rS pattern in V1-V6 R.

Figure 3

(A) Subcostal long-axis view showed the anterior ventricular septum and posterior wall were significantly thickened and a characteristic “granular sparkling” appearance of the thickened cardiac walls. (B) Subcostal 4-chamber view showed the ventricular septum and posterior lateral wall were significantly thickened and a characteristic “granular sparkling” appearance of the thickened cardiac walls. (C) Subcostal short axis view at the level of papillary muscle: all of the basal segments of ventricular wall were significantly thickened with a characteristic “granular sparkling” appearance. (D) The Bull’s eye diagram showed reduced global longitudinal strain (GLS) with apical sparing.

Figure 4

Display of chest CT images of the patient. Figure (A–C) were displayed on lung window at the top of the diaphragm at different times. The small calcification shadow on the lung surface at the base of both lungs gradually increased. In additional, they all showed diffuse pulmonary interstitial changes, cystic change and lung consolidation shadows. (D) Mediastinal window on the same plane as figure (A–C): fine sand granular calcification can be seen under the pleura in the lesion of the lower lobe of the left lung, which is clearer than that in the lung window.

Figure 5

TTR gene sequencing: A missense mutation c. 148 G-A (p. V50M, Val30Met) was detected in TTR gene.