Brazilian consensus for diagnosis, management and treatment of transthyretin familial amyloid polyneuropathy

Pinto, Marcus Vinicius; Barreira, Amilton Antunes; Bulle, Acary Souza; Freitas, Marcos R. G. de; França, Marcondes Cavalcante; Gondim, Francisco de Assis Aquino; Marrone, Carlo Domênico; Marques, Wilson; Nascimento, Osvaldo J. M.; Rotta, Francisco Tellechea; Pupe, Camila; Waddington-Cruz, Márcia

doi:10.1590/0004-282x20180094

Cited by 19 publications

(34 citation statements)

References 77 publications

(100 reference statements)

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“…The change in this paradigm is crucial, as probably the most common presentation of ATTRv-PN worldwide is of a length-dependent axonal peripheral neuropathy with pan-modality sensation loss [15]. As ATTRv-PN is a treatable disease [19], physicians should be aware of clues and red-flags for ATTR-PN in progressive undiagnosed peripheral neuropathies [19,20]. Differences in the clinical phenotype of early and late-onset Val30Met ATTR-PN have been described in Japan and Portugal, but little was known about these differences in Brazil before our study.…”

Section: Discussionmentioning

confidence: 99%

Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry

Pinto

Dias

et al. 2019

Journal of the Neurological Sciences

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Background: Despite growing numbers of patients diagnosed with late-onset hereditary ATTR V30M amyloidosis with polyneuropathy (ATTRv-PN), this condition remains poorly characterized in Brazil. Objective: Characterize late-onset V30M ATTRv-PN in Brazil. Material and methods: Demographic and clinical data at the time of enrolment for Brazilian subjects with symptomatic V30M ATTRv-PN were extracted from the ongoing, multinational, longitudinal, observational Transthyretin Amyloidosis Outcomes Survey (THAOS; cut-off date: January 30, 2017). Subjects were divided into those with symptom onset at age < 50 years (EO-V30M), and at age ≥50 years (LO-V30M). Results: A total of 96 Val30Met patients were symptomatic. LO-V30M (n = 25, 26.0%) had a longer time to diagnosis (mean 5.1 vs. 2.8 yrs.; p = 0.006) and less frequently positive family history (40% vs. 95.8%; p < 0.0001) than EO-V30M. Clinically, subjects with LO-V30M had more imbalance (92% vs. 54.9%; p = 0.006), deep sensory loss (100% vs. 80%; p = 0.0178), electrocardiogram abnormalities (88.9% vs. 59.4; p = 0.0241), and interventricular septum hypertrophy (69.2% vs. 0%; p < 0001) and less frequently sensory dissociation (12% vs. 74%; p < 0.0001). Also, LO-V30M tended to have more severe mean Neurologic Composite Score (101 vs. 70 pts.; p = 0.1136). Conclusions: LO-V30M ATTRv-PN is not unusual in Brazil, tending to be more difficult to diagnose and present with a more severe phenotype, with more large nerve fibers and cardiac involvement than EO-V30M.Trial Registration: ClinicalTrials.gov: NCT00628745

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Section: Discussionmentioning

confidence: 99%

Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry

Pinto

Dias

et al. 2019

Journal of the Neurological Sciences

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“…Other differential diagnoses of ATTR-FAP are diabetic neuropathy, inherited sensory and autonomic neuropathies, leprosy, toxic neuropathies, immunoglobulin light-chain amyloidosis and Fabry's disease. The Brazilian consensus on ATTR-FAP recommends that it should be strongly considered in patients with progressive polyneuropathy of unknown etiology who have one or more of the following: family history of neuropathy; orthostatic hypotension; erectile dysfunction; unexplained weight loss; arrhythmias and/or cardiomyopathy; bilateral carpal tunnel syndrome; renal abnormalities; vitreous opacities; gastrointestinal complaints (chronic diarrhea, constipation or diarrhea/constipation); rapid progression and/or prior treatment failure 17 .…”

Section: Discussionmentioning

confidence: 99%

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

Waddington-Cruz¹,

Pinto²,

Pinto³

et al. 2019

Arq. Neuro-Psiquiatr.

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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.

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“…ATTRv amyloidosis is caused by more than 130 missense pathogenic variants in the TTR gene in an autosomal dominant inheritance pattern with variable penetrance. 16 The incidence of disease varies across the globe, with an estimated incidence of 8.7 patients per million persons per year in Portugal 114 and of 0.3 cases per million persons per year in the United States. 3 The phenotypes are classified as neurological, cardiac, or mixed according to whether the presentation is exclusively neuropathy or cardiomyopathy or a combination of both.…”

Section: Attrvmentioning

confidence: 99%

Neuromuscular amyloidosis: Unmasking the master of disguise

2021

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Amyloidosis refers to an etiologically heterogeneous group of protein misfolding diseases, pathologically characterized by extracellular amyloid fibrils producing congophillic amorphous deposits in organs and tissues, which may lead to severe organ dysfunction and mortality. Clinical presentations vary and are often nonspecific, depending on what organs or tissues are affected. In systemic amyloidosis, the peripheral nervous system is commonly affected, whereas the skeletal muscles are only rarely involved. Immunoglobulin light chain (AL) amyloidosis and hereditary transthyretin (ATTRv) amyloidosis are the most frequent types of systemic amyloidosis involving the neuromuscular system. Localized amyloidosis can occur in skeletal muscle, so-called isolated amyloid myopathy. Amyloid neuropathy typically involves small myelinated and unmyelinated sensory and autonomic nerve fibers early in the course of the disease, followed by large myelinated fiber sensory and motor deficits. The relentlessly progressive nature with motor, painful sensory and severe autonomic dysfunction, profound weight loss, and systemic features are distinct characteristics of amyloid neuropathy. Amyloid myopathy presentation differs between systemic amyloidosis and isolated amyloid myopathy. Long-standing symptoms, distal predominant myopathy, markedly elevated creatine kinase level, and lack of peripheral neuropathy or systemic features are highly suggestive of isolated amyloid myopathy. In ATTR and AL amyloidosis, early treatment correlates with favorable outcomes. Therefore, awareness of these disorders and active screening for amyloidosis in patients with neuropathy or myopathy are crucial in detecting these patients in the everyday practice of neuromuscular medicine. Herein, we review the clinical manifestations of neuromuscular amyloidosis and provide a diagnostic approach to this disorder.

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Brazilian consensus for diagnosis, management and treatment of transthyretin familial amyloid polyneuropathy

Cited by 19 publications

References 77 publications

Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry

Late-onset hereditary ATTR V30M amyloidosis with polyneuropathy: Characterization of Brazilian subjects from the THAOS registry

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

Neuromuscular amyloidosis: Unmasking the master of disguise

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