Baseline disease characteristics in Brazilian patients enrolled in Transthyretin Amyloidosis Outcome Survey (THAOS)

Abstract

Transthyretin amyloidosis (ATTR) is characterized by the deposit of mutant or wild-type transthyretin that forms amyloid fibrils, which are extracellularly deposited within tissues and organs. Clinical manifestations of familial amyloid polyneuropathy vary according to the mutation, age at onset and geographical location. This study aimed to describe baseline disease characteristics of Brazilian patients with transthyretin familial amyloid polyneuropathy (ATTR-FAP) enrolled in the Transthyretin Amyloidosis Outcome Survey (THAOS). Methods: The THAOS is an international, noninterventional, longitudinal, observational, web-based registry designed to characterize ATTR. The outcome measures included demographics (age at symptom onset, gender, time from onset of symptoms to diagnosis, family history), genotype, and clinical characteristics (presence of amyloid deposit, frequency of misdiagnosis, presenting symptomatology). The analysis was conducted in a dataset from Brazilian patients (from November 2008 to January 2016). Results: One hundred and sixty participants (52.5% male) were included in the analysis. The majority of participants (90.6%) reported a positive family history of ATTR-FAP Median age at symptom onset was 32.5 years. Val30Met mutation was found in 91.9%. Misdiagnosis was observed in 26.6% of symptomatic patients. Over one-third (35.3%) of the misdiagnosed patients experienced a delay of more than one year before receiving a correct diagnosis. At presentation, 79.7% of the patients had motor, 87.5% sensory and 93.8% autonomic symptoms. Conclusion: ATTR-FAP in Brazil starts early, has a strong family history and the majority has Val30Met mutation. Misdiagnosis is common and the most common presentation is of a sensorimotor and autonomic neuropathy.

A Descriptive Analysis of ATTR Amyloidosis in Spain from the Transthyretin Amyloidosis Outcomes Survey

“…Over 30% of patients with the Val30Met variant experienced cardiac symptoms, with or without neurologic symptoms. Cardiac involvement has previously been reported to be present in similar proportions (30-36%) among patients with Val30Met [4,15,16,19] and, as expected, is more frequent among those patients with late-onset disease [4,15]. This reinforces the need for a multidisciplinary approach in endemic areas, independent of the most frequent phenotype of the area.…”

“…The neurologic phenotype was the predominant clinical picture of patients with ATTR amyloidosis in Spain, followed by the mixed phenotype. The neurologic phenotype is also predominant in other countries with endemic foci of patients with the Val30Met variant, including Portugal, Sweden, Japan, and Brazil [ 4 , 15 , 16 ]. The cardiac phenotype is more commonly seen in other European countries such as Germany, Denmark, and Italy, where there is a greater distribution of genotypes [ 4 ], and in the United States, where a large proportion of patients have ATTRwt amyloidosis or the Val122Ile (p.Val142Ile) mutation [ 17 ].…”

Posicionamento sobre Diagnóstico e Tratamento da Amiloidose Cardíaca – 2021

“…Estudos demonstram que 13% 21 dos pacientes com ICFEP e 25% das necropsias de idosos, 22,23 principalmente do sexo masculino, apresentam depósito de ATTR no coração. 24 Muito mais que uma doença rara, na verdade, a AC é uma condição subdiagnosticada. Dados recentes nos EUA registram o progressivo aumento na prevalência, aumentando de 18 para 55,2 (100.000 pessoas-ano), 25 e fortalecem o conceito da falta do diagnóstico que equivocadamente era considerado como inexistência da doença.…”

Neuromuscular amyloidosis: Unmasking the master of disguise

“…23 Pain and autonomic dysfunction are clinical hallmarks of amyloid neuropathy; although they can occur in CIDP, they do so less frequently and are milder. Pain occurs in 27%-74% of patients with amyloid neuropathy 14,24,25 and approximattely one-third of those with CIDP, 26 whereas autonomic symptoms occur in 65%-94% of patients with amyloid neuropathy 13,24,25,27 and 23% of patients with CIDP. 28 In CIDP, NCS usually show findings indicative of an acquired demyelinating neuropathy and EMG commonly shows diffuse chronic neurogenic changes and active denervation affecting both proximal and distal muscles (polyradiculoneuropathy).…”

“…However, the p.Val142Ile (Val122Ile) mutation is relatively common among African Americans (3.5%), 118 and in one study this mutation was found in 10% of African Americans older than 60 years of age with heart failure 119 . Interestingly, patients with p.Val50Met (Val30Met) mutation from Portugal, Brazil, and the southern part of Japan usually present with early‐onset (<50 years) profound autonomic neuropathy and small fiber sensory loss in the second or third decade of life, 120,121,27 whereas patients with same mutation from other regions present with late‐onset (>50 years) pan‐modality sensory loss and mild or no autonomic disturbance 15,122,123 . In ATTRv amyloidosis, the sensitivity of biopsy may vary with genotype and phenotype, but in general, fat aspirate is positive in approximately 45%, 110 lip biopsy in 75%‐91%, 124,125 and skin biopsy in 70% 126 .…”