Evaluation of a New Diagnostic Approach to Familial Amyloid Neuropathy by Mutation of the TTR Gene in a Population of Idiopathic Chronic Neuropathies
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Diagnosis of TTR-FAP
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
patients with chronic neuropathy of unknown aetiology
For the 130 patients with chronic neuropathy of unknown aetiology, the diagnosis of TTR-FAP will be performed using standard procedures following international recommendations, requiring genetic analysis of the TTR gene.
干预措施: Systematic screening of TTR mutations (Genetic)
结局指标
主要结局
Diagnosis of TTR-FAP
时间窗: 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
次要结局
- History of dysautonomias(at the inclusion visit)
- Age of patient at diagnosis(at the inclusion visit)
- Signs of dysautonomias(at the inclusion visit)
- Motor deficit of the lower limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS)(at the inclusion visit)
- Presence / Absence of reflexes osteo-tendinous evaluated by a subscore of the Neuropathy Impairment Scale (NIS)(at the inclusion visit)
- Rasch-built Overall Disability Scale (RODS) score(at the inclusion visit)
- Weight of patient(at the inclusion visit)
- Motor deficit of the upper limbs evaluated by a subscore of the Neuropathy Impairment Scale (NIS)(at the inclusion visit)
- Sensory deficit evaluated by a subscore of the Neuropathy Impairment Scale (NIS)(at the inclusion visit)
- Height of patient(at the inclusion visit)
- Presence of orthostatic hypotension(at the inclusion visit)
- Overall Neuropathy Limitations Scale (ONLS) score(at the inclusion visit)
- Electroneuromyography findings (ENMG): axonal, demyelinating or mixed neuropathy).(at the inclusion visit)
- Dysautonomia score(at the inclusion visit)