Amyloidogenic transthyretin Val30Met homozygote showing unusually early-onset familial amyloid polyneuropathy

2008 ◽  
Vol 37 (6) ◽  
pp. 796-803 ◽  
Author(s):  
Kana Tojo ◽  
Yoshiki Sekijima ◽  
Kazuko Machida ◽  
Ayako Tsuchiya ◽  
Masahide Yazaki ◽  
...  
Keyword(s):  
Early Onset ◽  
Familial Amyloid Polyneuropathy ◽  
Amyloid Polyneuropathy

Extremely Early Onset Transthyretin Familial Amyloid Polyneuropathy with a Leu55Pro Mutation: A Pediatric Case Report and Literature Review

2019 ◽  
Vol 50 (05) ◽  
pp. 322-326
Author(s):  
Yun Jeong Lee ◽  
Jeeyoung Oh ◽  
Su-Kyeung Hwang ◽  
Eun Joo Lee ◽  
Dong Heon Yang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Early Onset ◽  
Orthostatic Intolerance ◽  
Subcutaneous Fat ◽  
Gastrointestinal Symptoms ◽  
Familial Amyloid Polyneuropathy ◽  
Pediatric Case ◽  
Limb Weakness ◽  
Amyloid Polyneuropathy ◽  
Transthyretin Familial Amyloid Polyneuropathy

AbstractTransthyretin familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant disease caused by the deposition of amyloid fibrils composed of TTR proteins. Symptoms of this disease include progressive sensorimotor neuropathy, cardiomyopathy, and involvement of other organs. We described a pediatric case of extremely early onset TTR-FAP with a TTR Leu55Pro mutation. A 17-year-old boy began to suffer from lower limb weakness, gait disturbance, and decreased sensation from 14 years of age onward. He presented with hypertrophic cardiomyopathy, periorbital and scleral ecchymosis, anhidrosis, orthostatic intolerance, and gastrointestinal autonomic dysfunction including nausea, vomiting, and diarrhea alternating with constipation. The patient's older sister had developed similar gastrointestinal symptoms from 20 years of age onward and was diagnosed as having hypertrophic cardiomyopathy. The boy's biopsy results showed infiltrated amyloid deposition on subcutaneous fat tissue and endocardium. Genetic analysis of the TTR gene demonstrated that both the patient and his sister had a pathogenic mutation, c.224T > C (Leu55Pro). Both patients were prescribed tafamidis, a TTR stabilizing agent. Although a majority of TTR-FAPs occur during adulthood, it should be suspected, even in pediatric populations, when symmetric length dependent neuropathy occurs in conjunction with a family history of neuropathy, autonomic neuropathy, and/or cardiomyopathy.

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

2015 ◽  
Vol 10 (S1) ◽  
Author(s):  
Manuel Raya-Cruz ◽  
Juan Buades-Reines ◽  
Cristina Gallego-Lezaun ◽  
Ignacio Ferullo ◽  
Tomas Ripoll-Vera ◽  
...  
Keyword(s):  
Early Onset ◽  
Familial Amyloid Polyneuropathy ◽  
Amyloid Polyneuropathy ◽  
Transthyretin Familial Amyloid Polyneuropathy

scholarly journals mtDNA copy number associated with age of onset in familial amyloid polyneuropathy

2017 ◽  
Vol 89 (3) ◽  
pp. 300-304 ◽  
Author(s):  
Diana Santos ◽  
Maria João Santos ◽  
Miguel Alves-Ferreira ◽  
Teresa Coelho ◽  
Jorge Sequeiros ◽  
...  
Keyword(s):  
Early Onset ◽  
Copy Number ◽  
Age Of Onset ◽  
Age At Onset ◽  
Familial Amyloid Polyneuropathy ◽  
Mtdna Copy Number ◽  
Potential Biomarker ◽  
Amyloid Polyneuropathy ◽  
First Time

BackgroundTransthyretin-related familial amyloid polyneuropathy (TTR-FAP Val30Met) shows a wide variation in age-at-onset (AO) between generations and genders, as in Portuguese families, where women display a later onset and a larger anticipation (>10 years). Mitochondrial DNA (mtDNA) copy number was assessed to clarify whether it has a modifier effect on AO variability in Portuguese patients.MethodsThe mtDNA copy number of 262 samples (175 Val30Met TTR carriers and 87 controls (proven Val30Val)) was quantified by quantitative real-time PCR. Statistical analysis was performed using IBM SPSS V.23 software.ResultsThis study shows that Val30Met TTR carriers have a significantly higher (p<0.001) mean mtDNA copy number than controls. Furthermore, the highest mtDNA copy number mean was observed in early-onset patients (AO <40 years). Importantly, early-onset offspring showed a significant increase (p=0.002) in the mtDNA copy number, when compared with their late AO parents.ConclusionsThe present findings suggest, for the first time, that mtDNA copy number may be associated with earlier events and may therefore be further explored as a potential biomarker for follow-up of TTR-FAP Val30Met carriers.

scholarly journals Clinicopathological correlations of sural nerve biopsies in TTR Val30Met familial amyloid polyneuropathy

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Armindo Fernandes ◽  
Teresa Coelho ◽  
Aurora Rodrigues ◽  
Helena Felgueiras ◽  
Pedro Oliveira ◽  
...  
Keyword(s):  
Early Onset ◽  
Sural Nerve ◽  
Nerve Biopsy ◽  
Amyloid Deposition ◽  
Familial Amyloid Polyneuropathy ◽  
Asymptomatic Carriers ◽  
Mutation Carriers ◽  
Amyloid Polyneuropathy ◽  
Myelinated Fibres ◽  
Fibre Loss

Abstract Familial amyloid polyneuropathy with the substitution of methionine for valine at position 30 in the TTR gene is the most common type of hereditary transthyretin amyloidosis. Although several authors have previously reported a size-dependent fibre loss, predominantly involving unmyelinated and small-diameter myelinated fibres, the mechanisms of nerve fibre loss have not been fully understood. In this study, we establish the morphometric pattern of peripheral neuropathy in patients with familial amyloid polyneuropathy and asymptomatic mutation carriers in the biopsies from our archive and correlated the pathological findings with clinical features. A total of 98 patients with familial amyloid polyneuropathy and 37 asymptomatic mutation carriers (TTR Val30Met mutation), aged between 17 and 84 years, who underwent sural nerve biopsy between 1981 and 2017 at Centro Hospitalar Universitário do Porto were studied. Thirty-one controls were included for comparison. The median age at nerve biopsy was 26.0 [interquartile range = 23.5–39.5] years for asymptomatic mutation carriers, 45.0 [35.0–60.0] years for patients with familial amyloid polyneuropathy and 44.0 [30.0–63.0] years for controls. The median duration between nerve biopsy and symptoms’ onset was 7.0 [3.3–11.8] years (range: 1–27 years) in the asymptomatic carriers. Most patients were in an earlier disease stage (93% with a polyneuropathy disability scale ≤2). Patients had loss of small and myelinated fibres compared with both asymptomatic carriers and controls (P &lt; 0.001), whereas asymptomatic carriers showed loss of small myelinated fibres when compared with controls (P &lt; 0.05). The loss of myelinated fibres increased with disease progression (P &lt; 0.001), and patients in more advanced clinical stage showed more frequent amyloid deposition in the nerve (P = 0.001). There was a positive correlation between large myelinated fibre density and time to symptoms’ onset in the asymptomatic carriers that developed early-onset form of the disease (r = 0.52, P &lt; 0.01). In addition, asymptomatic carriers with amyloid deposition already present in sural nerve biopsies developed symptoms earlier than those with no amyloid (P &lt; 0.01). In conclusion, this study confirms that the loss of small fibre size is an initial event in familial amyloid polyneuropathy, already present in asymptomatic gene carriers, starting several years before the onset of symptoms. We show for the first time that large myelinated fibres’ loss and amyloid deposition are pathological features that correlate independently with short period to the onset of symptoms for asymptomatic carriers that developed early-onset form of the disease. These findings are therapeutically relevant, as it would allow for a better interpretation of the role of disease-modifying agents in transthyretin familial amyloid polyneuropathy.

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

2016 ◽  
Vol 21 (4) ◽  
pp. 352-356 ◽  
Author(s):  
Juan Buades-Reinés ◽  
Manuel Raya-Cruz ◽  
Cristina Gallego-Lezaún ◽  
Tomás Ripoll-Vera ◽  
Mercedes Usón-Martín ◽  
...  
Keyword(s):  
Early Onset ◽  
Familial Amyloid Polyneuropathy ◽  
Amyloid Polyneuropathy ◽  
Transthyretin Familial Amyloid Polyneuropathy
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