Amyloid Neuropathies, Familial
Conditions
Keywords
proportion, TTR-FAP, study, neuropathy
Brief summary
TTR-FAP is a rare disabling inherited disorder that predominantly affects the peripheral nervous system and the heart. Due to an important phenotypic and genetic heterogeneity, the diagnosis is often delayed, preventing therefore early onset treatment. Our project is to evaluate the prevalence of TTR-FAP in a series of 130 patients with from chronic neuropathy of undetermined aetiology through a systematic screening of TTR mutations.
Detailed description
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder, highly disabling and life-threatening, resulting of transthyretin (TTR) gene mutation. Clinically, TTR FAP is characterized by progressive sensorimotor and dysautonomic neuropathy, usually fatal within a few years. The disease prevalence is highly variable, with a large genotypic and phenotypic heterogeneity. Early and accurate diagnosis remains essential to propose early treatment. New pharmacotherapies have been developed, such as Tafamidis®, and many patients can avoid liver transplant formerly considered as the only therapeutic option. The prevalence of TTR-FAP disease has been previously estimated in series of patients with severe and progressive neuropathy, frequently leading to a delayed diagnosis. TTR-FAP is also easily suspected when neuropathy is associated with cardiac symptoms or dysautonomia. Currently, genetic testing of TTR-FAP is targeted and is only prescribed to patients in whom the first-line assessment recommended by the High Authority for Health (HAS) did not identify a cause, and on the basis of a worsening of symptoms. An early diagnosis in those cases would allow earlier treatment and monitoring. No data are available about the prevalence of TTR-FAP in populations of patients with from chronic neuropathy of unknown aetiology, through a systematic screening of TTR mutations. The diagnosis of TTR-FAP will be performed using standard procedures following international recommendations, requiring genetic analysis of the TTR gene. The patients with a diagnosis of TTR-FAP confirmed during this study will be seen for an additional visit in the Investigating Centre and proposed suitable follow up, treatment and care.
Interventions
GENETICSystematic screening of TTR mutations
The diagnosis of TTR-FAP requires genetic analysis using direct sequencing of TTR gene.The diagnosis of TTR-FAP will be performed using standard procedures following international recommendations, requiring genetic analysis of the TTR gene.
Sponsors
University Hospital, Bordeaux
University of Bordeaux
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Patients of both sexes presenting chronically (\> 3 months): * neuropathy confirmed by an electroneuromyography * without obvious etiology (diabetes, alcohol consumption, renal insufficiency, neurotoxic substances intake, family history of diagnosed hereditary neuropathy) * without anomaly of the following biological examinations: fasting blood glucose, blood count, gamma-glutamyl transferases, average cell volume, transaminases, serum creatinine clearance, C-reactive protein, TSH * Aged 18 to 90 years Patients giving their free and informed consent to participate, after research information
Exclusion criteria
* People placed under the protection of justice. * Patients who are not affiliated or who are not beneficiaries of a social security scheme * Patients with chronic neuropathy related to a known etiology
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnosis of TTR-FAP | Genetic analyzes will be performed every three months from the first inclusion | Proportion of TTR-FAP in the 130 patients with chronic neuropathy of unknown aetiology |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Age of patient at diagnosis | at the inclusion visit | — |
| History of dysautonomias | at the inclusion visit | History of dysautonomias at the interview |
| Signs of dysautonomias | at the inclusion visit | signs of dysautonomias at the interview |
| Weight of patient | at the inclusion visit | weight |
| Height of patient | at the inclusion visit | height |
| Motor deficit of the lower limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS) | at the inclusion visit | The Motor deficit of the lower limbs will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the NIS scale is 244 points. The motor sub score, including the evaluation of the upper and lower limbs, is scored on 192 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 4 points. |
| Motor deficit of the upper limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS) | at the inclusion visit | The Motor deficit of the upper limbs will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the scale is 244 points. The motor sub score, including the evaluation of the upper and lower limbs, is scored on 192 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 4 points. |
| Sensory deficit evaluated by a subscore of the Neuropathy Impairment Scale (NIS) | at the inclusion visit | The Sensory deficit will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the scale is 244 points. The sensory sub score is scored on 20 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 2 points. |
| Presence / Absence of reflexes osteo-tendinous evaluated by a subscore of the Neuropathy Impairment Scale (NIS) | at the inclusion visit | The Presence/Absence of reflexes osteo-tendinous will be assessed through a sub score of the Neuropathy Impairment Scale (NIS). The maximum score on the scale is 88 points. The reflexes sub score is scored on 8 points. This scale allows to obtain a quantification of the clinical examination. Each item is evaluated between 0 and 2 points. |
| Presence of orthostatic hypotension | at the inclusion visit | Blood pressure measurement by the nurse |
| Dysautonomia score | at the inclusion visit | Score at the clinical scale assessing autonomic dysfunction according to 5 modalities: orthostatic hypotension, high digestive motor disorders, low digestive motor disorders, vesicosphincteric disorders, erectile dysfunction |
| Rasch-built Overall Disability Scale (RODS) score | at the inclusion visit | Score at the RODS, a functional scale that captures daily activity and social participation limitations in patients affected by polyneuropathy (self-questionnaire) |
| Overall Neuropathy Limitations Scale (ONLS) score | at the inclusion visit | The ONLS is a validated neuropathy functional scale evaluating the performance of upper and lower cells. The upper limbs sub score is scored on 5 points and the lower limbs sub score is scored on 7 points. The scale thus ranges from 0 (no disability) to 12 points (disability maximum) |
| Electroneuromyography findings (ENMG): axonal, demyelinating or mixed neuropathy). | at the inclusion visit | — |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORGuilhem Solé, MD
University Hospital Bordeaux, France
Outcome results
None listed