Castellar-Leones Sandra Milena, Ruiz-Ospina Edicson, Diaz-Ruiz Jorge, Correa-Arrieta Cristian, Ruiz-Cortés Xiomara, Luzuriaga-Carpio Diana, Zambrano-Vera Dario, Cedeño-Quincha Jeanneth, Guerrero-Cepeda Luis, César-Chávez Daniel, Ortiz-Corredor Fernando
Department of Physical Medicine and Rehabilitation, Facultad de Medicina, Universidad Nacional de Colombia, Carrera 30 No.45-03. Edificio 471, Piso 5to, Of. 513-A, Bogotá, Colombia.
Research Center for Physiatry and Electrodiagnostics, (CIFEL), Bogotá, Colombia.
Orphanet J Rare Dis. 2024 Dec 20;19(1):474. doi: 10.1186/s13023-024-03496-0.
Hereditary transthyretin amyloidosis (hATTR) is a rare autosomal dominant disease with high clinical variability, influenced by both genotype and the geographic origins of carriers. There is a limited understanding of the Val142Ile and Ser43Asn recognised mutations in Ecuador and Colombia. Therefore, the objective of this study is to describe the neurological and functional characteristics of patients with hATTR associated with the Val142Ile and Ser43Asn mutations, as well as to identify possible differentiating factors between the two mutations.
This cross-sectional, multicenter study included 35 hATTR patients from rehabilitation centers in Ecuador and Colombia. Patients had confirmed Val142Ile or Ser43Asn mutations. Neurological and functional assessments included the Neurological Impairment Scale, Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN), Composite Autonomic Symptom Score-31, and various motor function tests as nine-hole peg test (NHP). Quantitative Sensory Testing (QST) evaluating small fiber function, while ultrasound measured the cross-sectional area (CSA) of peripheral nerves. Statistical analysis employed nonparametric tests and random forest classifiers, using SHAP values to identify differentiating variables.
Val142Ile carriers showed lower performance in the right NHP test and greater sensitivity to cold pain in hand and leg. Ultrasound revealed increased CSA of the median nerve at the elbow and arm and the ulnar nerve at the arm in Val142Ile carriers compared to Ser43Asn carriers. The final random forest model identified the NHP test, Norfolk QOL-DN score, and CSA of the median and ulnar nerves as key discriminating variables.
This study identified significant neurophysiological and ultrasound markers differentiating Val142Ile and Ser43Asn mutations in hATTR-PN patients. Increased nerve CSA and specific motor and sensory impairments highlight the need for comprehensive evaluations to guide diagnosis and treatment.
遗传性转甲状腺素蛋白淀粉样变性（hATTR）是一种罕见的常染色体显性疾病，临床变异性高，受基因型和携带者的地理来源影响。对厄瓜多尔和哥伦比亚所识别出的Val142Ile和Ser43Asn突变的了解有限。因此，本研究的目的是描述与Val142Ile和Ser43Asn突变相关的hATTR患者的神经和功能特征，并确定这两种突变之间可能的鉴别因素。
这项横断面、多中心研究纳入了来自厄瓜多尔和哥伦比亚康复中心的35例hATTR患者。患者已确诊Val142Ile或Ser43Asn突变。神经和功能评估包括神经损伤量表、诺福克糖尿病神经病变生活质量量表（QOL-DN）、自主神经症状综合评分-31，以及各种运动功能测试，如九孔插针试验（NHP）。定量感觉测试（QST）评估小纤维功能，而超声测量周围神经的横截面积（CSA）。统计分析采用非参数检验和随机森林分类器，使用SHAP值来识别鉴别变量。
Val142Ile携带者在右侧NHP测试中的表现较低，对手部和腿部的冷痛更敏感。超声显示，与Ser43Asn携带者相比，Val142Ile携带者肘部和手臂的正中神经以及手臂的尺神经的CSA增加。最终的随机森林模型将NHP测试、诺福克QOL-DN评分以及正中神经和尺神经的CSA确定为关键鉴别变量。
本研究确定了区分hATTR-PN患者中Val142Ile和Ser43Asn突变的重要神经生理学和超声标志物。神经CSA增加以及特定的运动和感觉障碍突出了进行全面评估以指导诊断和治疗的必要性。
