Late-Onset Familial Amyloid Polyneuropathy (FAP) Val30Met Without Family History

Abstract

Familial amyloid polyneuropathy (FAP) is rare and most commonly caused by the Val30Met mutation of the transthyretin (TTR) gene. Beside polyneuropathy, other complications due to amyloid deposits occur, but may vary in phenotype. The mutation tends to occur in endemic clusters.We describe a 65-year-old man from a non-endemic FAP Val30Met area who developed a progressive generalized painless axonal sensorimotor polyneuropathy with mild autonomic involvement and absent FAP symptoms in the family. Nerve biopsy showed amyloid deposits, staining with TTR-antibodies on immunohistochemistry.After DNA-sequencing of the TTR gene, the diagnosis of FAP Val30Met was made. Late-onset FAP Val30Met is a progressive and fatal disorder with varying penetrance, and may occur in non-endemic areas and cases without a family history.

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series

“…This may be manifested by motor impairment, muscle weakness and wasting, and multiple organ failure, but the disease is phenotypically heterogeneous [6]. In nearly all cases ATTR-PN will progress and lead to loss of bodily function, diminished quality of life, and death within approximately 10–15 years after onset, often due to cardiac complications [7–11].…”

Uma causa rara de hipertensão arterial secundária

“…No entanto, existem alguns casos de início tardio da doença descritos na literatura científica. 13 Um dos pontos a favor do diagnóstico de PAF num indivíduo é a história familiar. No entanto, em 13% dos casos podem não existir antecedentes familiares.…”

“…No entanto, em 13% dos casos podem não existir antecedentes familiares. 13 Neste caso clínico a utente apenas soube informar que a sua mãe também era hipertensa e que faleceu já a realizar hemodiálise, situação que leva a suspeitar que, provavelmente, esta também sofreria de PAF. O único familiar que actualmente demonstrou interesse em realizar investigação complementar foi o filho da utente, que já foi consultado no Hospital de Santo António.…”

The role of fibrinogen glycation in ATTR: evidence for chaperone activity loss in disease

“…Although TTR tetramer stability may be a significant factor in the initiation of amyloid fibril formation, there are a number of observations related to ATTR pathogenesis that must be considered in order to have a solid understanding of this disease. First, mutant TTR, which is present from birth does not evolve to amyloid fibril prior to late adult life [10][11][12]. It is unreasonable to consider that the late onset of the disease is only due to tetramer destabilization, since the mutant protein is present from birth [10][11][12].…”

“…First, mutant TTR, which is present from birth does not evolve to amyloid fibril prior to late adult life [10][11][12]. It is unreasonable to consider that the late onset of the disease is only due to tetramer destabilization, since the mutant protein is present from birth [10][11][12]. Second, wild-type TTR presents intrinsic amyloidogenicity, since its aggregation in older individuals causes Systemic Senile Amyloidosis (SSA) [13].…”