Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

Abstract

BackgroundThe disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical.MethodsWe retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center.ResultsEight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%).ConclusionsThis study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s12883-017-0957-4) contains supplementary material, which is available to authorized users.

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

“…Gastrointestinal dysfunctions and orthostatic intolerance were the most prevalent autonomic complaints. Gastrointestinal symptoms seemed to present in the early phase of disease, like previous studies [ 7 , 10 , 20 ]. Sudomotor dysfunction, though frequently evident by neurophysiological tests (the results of 7/7 QSART tested patients were abnormal.…”

“…Motor neuropathy appeared in the later stage of disease and was usually accompanied by significant weight reduction. Weight reduction has been hypothesized to be due to gastrointestinal dysautonomia, dysphagia and muscular atrophy [ 7 ]. Of interest, our study showed that when motor neuropathy was present, the overall worsening of neuropathy tended to progress faster than when motor neuropathy was not present in both clinical and neurophysiological aspects (Table 2 ).…”

“…Of interest, the age of onset appeared lower in this cohort and neuropathy can be evident in middle adulthood. ATTRA97S-PN has usually been found to manifest with late-onset (> 50 years) polyneuropathy [ 4 , 6 , 7 ]. However, two reported patients from mainland China had early-onset (38 and 23 years) disease [ 18 , 19 ].…”

“…AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3)(4)(5)(6)(7)(8)(9).…”

Orthostatic hypotension in hereditary transthyretin amyloidosis: epidemiology, diagnosis and management

“…OH is also prevalent and severe in patients with some non-Val30Met mutations [12, 15, 20, 24, 25, 27, 49, 53, 57, 60, 69, 73, 78, 79, 95, 96, 113, 115, 119, 136, 137, 142, 145]. For instance, up to 100% of patients with the Ala97Ser mutation have OH, with 71% having frequent syncope, particularly in late stages of the disease [58].…”