Servicio de Neurología, Hospital Universitario Central de Asturias, Spain.
Servicio de Neurología, Hospital Universitario Central de Asturias, Spain; Instituto de Investigación Sanitaria del Principado de Asturias, Spain.
J Neurol Sci. 2021 Jun 15;425:117452. doi: 10.1016/j.jns.2021.117452. Epub 2021 Apr 16.
Intermediate Alleles (IAs) are expansions of CAG repeats in the HTT gene between 27 and 35 repeats which pathogenic meaning remains controversial. They are present in the general population but there is an increasing number of cases with Huntington-like phenotype reported.
We reviewed the medical records of cases in our centre where the neurologist suspected Huntington's disease (HD) as one of the feasible diagnoses and genetic testing showed the number of CAG repeats was in the "intermediate range". We gathered the type of symptoms in all cases and the main neuroimaging findings when available.
We found 14 cases, 8 males and 6 females, with average age at onset at 64 years old. Most cases exhibited some type of extrapyramidal symptoms. Cognitive and/or behavioral symptoms were also present in most cases (being depression, anxiety and cognitive impairment the most frequent ones). In one case we found deposits of iron in the basal ganglia in the MRI, and in another case we found diffuse cortical hypometabolism with predominantly frontal bilateral involvement and bilateral focal deficit of both caudate and thalamus in the FDG-PET.
The clinical and neuroimaging findings of some cases with IA in this series are compatible with the clinical picture of HD but also with several other alternative diagnoses. Therefore we can not establish association between IA and HD. Larger series with more comprehensive diagnostic workout and neuropathological studies are needed to confirm or rule out whether IAs in the HTT gene may cause HD.
中间等位基因（IAs）是 HTT 基因中 CAG 重复扩展，其致病性意义仍存在争议。它们存在于普通人群中，但越来越多的具有亨廷顿样表型的病例被报道。
我们回顾了我们中心的病例的医疗记录，神经科医生怀疑这些病例是亨廷顿病（HD）的一种可能诊断，基因检测显示 CAG 重复次数处于“中间范围”。我们收集了所有病例的症状类型和主要神经影像学发现（如有）。
我们发现了 14 例病例，8 例男性，6 例女性，发病平均年龄为 64 岁。大多数病例表现出某种类型的锥体外系症状。大多数病例也存在认知和/或行为症状（最常见的是抑郁、焦虑和认知障碍）。在一例病例中，我们在 MRI 中发现基底节有铁沉积，在另一例病例中，我们发现 FDG-PET 显示弥漫性皮质代谢低下，主要累及双侧额区，双侧尾状核和丘脑局限性缺陷。
本系列中一些具有 IA 的病例的临床和神经影像学发现与 HD 的临床表现一致，但也与其他一些替代诊断一致。因此，我们不能确定 IA 与 HD 之间存在关联。需要更大的系列，更全面的诊断方法和神经病理学研究，以确认或排除 HTT 基因中的 IA 是否可能导致 HD。
