Vitreous Amyloidosis as the Presenting Symptom of Familial Amyloid Polyneuropathy TTR Val30Met in a Portuguese Patient

Seca, Mariana; Ferreira, Natália; Coelho, Teresa

doi:10.1159/000360790

Cited by 15 publications

(10 citation statements)

References 29 publications

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“…In addition to cardiac symptoms, renal, and ophthalmologic symptoms were also more common in the late AO group in this study, with the proportion of patients with dry eye and vitreous opacities significantly increased. These symptoms have classically been considered a signal of a potential severe systemic disease (Seca et al, ) . The rate of mortality was greater in the late AO group, and a slightly higher proportion of these deaths were related to hATTR compared with the early AO group; these data are fitting with the reduced survival expected in late AO patients (Koike et al, ) .…”

Section: Discussionmentioning

confidence: 99%

Transthyretin familial amyloid polyneuropathy (TTR‐FAP) in Mallorca: a comparison between late‐ and early‐onset disease

Buades-Reinés

Raya‐Cruz

Gállego-Lezáun

et al. 2016

J Peripheral Nervous Sys

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The age of onset (AO) of hereditary ATTR amyloidosis (hATTR) is known to vary between populations, with differing characteristics reported according to AO in endemic/non‐endemic foci. This was a retrospective study of patients with early AO (<50 years) and late AO (≥50 years) hATTR at our center in Mallorca. Data were collected on patient demographics, clinical disease manifestation, and physical symptoms. A total of 95 patients were analyzed, with mean follow‐up of 9 years from diagnosis. The early AO group included 53 patients (33 male) and the late AO group included 42 patients (21 male). Neurologic involvement was the most common initial symptom, although it was significantly more frequent in the late AO vs. early AO group (p = 0.015). Autonomic involvement was observed in 26% of patients in the early AO group, but was rarely observed in the late AO group (5%). During follow up, cardiologic symptoms, renal involvement, and ophthalmologic symptoms were significantly more common in the late AO group (p < 0.05). This retrospective study demonstrates the variation in disease presentation and progression according to AO of hATTR at our Mallorcan center.

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Section: Discussionmentioning

confidence: 99%

Transthyretin familial amyloid polyneuropathy (TTR‐FAP) in Mallorca: a comparison between late‐ and early‐onset disease

Buades-Reinés

Raya‐Cruz

Gállego-Lezáun

et al. 2016

J Peripheral Nervous Sys

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“…Physicians likely to diagnose and treat patients with this disease include neurologists, cardiologists, gastroenterologists, ophthalmologists, and other specialists (Ando et al, 2013). The age of onset varies between the 20s and the 90s (Seca, Ferreira, & Coelho, 2014). Lemos and colleagues (2014) consider that early-onset (≤ 40 years) and later-onset (≥ 50 years) cases of TTR-FAP V30M are not different entities, often coexisting in the same family, and showing anticipation, with earlier age-at-onset in younger generations, usually associated with more severe phenotype.…”

Section: The Studied Diseasesmentioning

confidence: 99%

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

Leite¹,

Denis²,

Sequeiros³

et al. 2017

Interd

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resUMenEl papel del psicólogo clínico en el contexto del consejo genético incluye brindar apoyo a los sujetos en riesgo en el proceso de toma de decisiones, independientemente de la decisión adoptada por el sujeto (conociendo o no el resultado de las pruebas genéticas).El estudio que se informa aborda la motivación para realizar las pruebas pre-sintomáticas (PPS) de sujetos en situación de riesgo para tres enfermedades: polineuropatía amiloide familiar (PAF), la enfermedad de Huntington (EH) y la enfermedad de Machado-Joseph (EMJ) y comparar con la motivación para realizar las PPS para hemocromatosis (HH).La muestra consistió en 213 sujetos portugueses que tenían riesgo genético para contraer las tres enfermedades y 31 sujetos en situación de ries go genético para contraer hemocromatosis. Ellos fueron evaluados con una entrevista para ob tener datos sociodemográficos y debían responder a una pregunta sobre la motivación para llevar a cabo las pruebas pre-sintomáticas.Se obtuvieron siete categorías principales y las las siguientes son las más significativas para PAF, EH y EMJ: razones relacionadas con el futuro, razones relacionadas con los demás y razones relacionadas con la curiosidad y la necesidad de conocer. Para hemocromatosis, las más importantes resultaron ser razones relacionadas con los demás y las relacionadas con las características de la enfermedad.La motivación para realizar el test pre-sintomático (PST) de la PAF, EH y EMJ es externa y sin relación con la enfermedad, mientras que la motivación de los sujetos en situación de riesgo para la HH está relacionada con la enfermedad. Las razones relacionadas con los demás es una motivación común en ambos grupos. A los sujetos también les preocupa la posibilidad de transmitir la enfermedad a sus hijos.Palabras clave: Pruebas pre-sintomáticas (PPS); Enfermedad genética; Sujetos en situación de riesgo; Polineuropatía amiloide familiar (PAF) TTR V30M; Enfermedad de Huntington (EH); Enfermedad de Machado-Joseph (EMJ). aBstraCtThe role of the clinical psychologist in the context of genetic counseling includes support for the process of decision-making for subjects at-risk, regardless of the decision that was made. For this,

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“…Patients with certain mutations, such as V122I, present predominantly with a cardiomyopathy (10), whereas other mutation carriers exhibit predominant involvement of the peripheral nervous system (11, 12), such as the V30M mutation associated with Familial Amyloid Polyneuropathy (FAP). Although the initial disease phenotype depends partially on the inherited TTR sequences (13), variability in clinical presentation is seen between patients with the same mutation and even within the same kindred, and some patients present with clinical manifestations in less commonly involved organs, such as the eye (14) (vitreous opacities and glaucoma), the central nervous system (15) (stroke and dementia) or the kidney (16) (nephrotic syndrome and chronic renal insufficiency). This poorly understood phenotypic variability or tissue tropism poses a considerable diagnostic challenge.…”

Section: Introductionmentioning

confidence: 99%

Peptide probes detect misfolded transthyretin oligomers in plasma of hereditary amyloidosis patients

et al. 2017

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Increasing evidence supports the hypothesis that soluble misfolded protein assemblies contribute to the degeneration of post-mitotic tissue in amyloid diseases. However, there is a dearth of reliable non-antibody based probes for selectively detecting oligomeric aggregate structures circulating in plasma or deposited in tissues, making it difficult to scrutinize this hypothesis in patients. Hence, understanding the structure-proteotoxicity relationships driving amyloid diseases remains challenging, hampering the development of early diagnostic and novel treatment strategies. Here, we report peptide-based probes that selectively label misfolded transthyretin (TTR) oligomers circulating in the plasma of TTR hereditary amyloidosis patients exhibiting a predominant neuropathic phenotype. These probes revealed that there are much fewer misfolded TTR oligomers in healthy controls, in asymptomatic carriers of mutations linked to amyloid polyneuropathy, and in patients with TTR-associated cardiomyopathies. The absence of misfolded TTR oligomers in the plasma of cardiomyopathy patients suggests that the tissue tropism observed in the TTR amyloidoses is structure based. Misfolded oligomers decrease in TTR amyloid polyneuropathy patients treated with disease-modifying therapies (tafamidis or liver transplant-mediated gene therapy). In a subset of TTR amyloid polyneuropathy patients, the probes also detected a circulating TTR fragment that disappeared after tafamidis treatment. Proteomic analysis of the isolated TTR oligomers revealed a specific patient associated-signature comprised of proteins that likely associate with the circulating TTR oligomers. Quantification of plasma oligomer concentrations using peptide probes could become an early diagnostic strategy, a response-to-therapy biomarker, and a useful tool for understanding structure-proteotoxicity relationships in the TTR amyloidoses.

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Vitreous Amyloidosis as the Presenting Symptom of Familial Amyloid Polyneuropathy TTR Val30Met in a Portuguese Patient

Cited by 15 publications

References 29 publications

Transthyretin familial amyloid polyneuropathy (TTR‐FAP) in Mallorca: a comparison between late‐ and early‐onset disease

Transthyretin familial amyloid polyneuropathy (TTR‐FAP) in Mallorca: a comparison between late‐ and early‐onset disease

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

Peptide probes detect misfolded transthyretin oligomers in plasma of hereditary amyloidosis patients

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