Familial Transthyretin Amyloidosis with Variant Asp38Ala Presenting with Orthostatic Hypotension and Chronic Diarrhea

Abstract

A 53-year-old man complained of orthostatic, non-rotating dizziness, and chronic watery diarrhea of several years duration. His nerve-conduction velocity test revealed peripheral sensory-motor polyneuropathy and he showed an autonomic function abnormality. Echocardiographic examination showed ventricular and atrial wall thickening with a granular "sparkling" appearance. Left ventricular systolic function was preserved but pseudonormal diastolic dysfunction was present. Coronary angiography showed normal coronary arteries and an endomyocardial biopsy revealed lesions consistent with cardiac amyloidosis. Colonoscopic biopsy also revealed the deposition of amyloid fibrils. Gene analysis found the transthyretin variant Asp38Ala. His son had same mutation, but three daughters did not. In conclusion, we report a case of familial transthyretin amyloidosis with Asp38Ala.

Keywords: Amyloidosis; Asp38Ala; Orthostatic hypotension; Polyneuropathy; Transthyretin.

Fig. 1

Two-dimensional transthoracic echocardiography. Biventricular hypertrophy and the thickened inter-atrial septum are shown in a parasternal long-axis view (A), four-chamber view (B and C).

Fig. 2

Pulse-waved Doppler echocardiogram (A) and tissue Doppler echocardiogram (B) showing and elevated E/Ea ratio and low mitral annulus velocities, suggestive of diastolic dysfunction with a pseudonormal pattern.

Fig. 3

Light microscopy finding of tissue obtained by cardiac biopsy (haematoxylin and eosin stained, original magnification × 40). Amyloid appears as pink-hyaline extracellular deposits (black arrows) between myocytes and in blood vessels.

Fig. 4

Electron microscopy of cardiac tissue. Electron microscopy demonstrated fibrils typical of amyloid at the edge of a myocytes (A). The edge of a myocyte (lower left) and above it is a mass of amyloid fibrils (B).

Fig. 5

Transthyretin gene analysis in the patient and his offspring (A: patient, B: daughter 1, C: daughter 2, D: daughter 3, E: son). A: The patient was diagnosed as transthyretin amyloidosis (ATTR) variant Asp38Ala. E: The patient's offspring were screening for ATTR, but only his son had the same mutation.