Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Medical Genetics Division, Department of Pediatrics, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
Eur J Neurol. 2023 Oct;30(10):3400-3403. doi: 10.1111/ene.15982. Epub 2023 Jul 19.
Defects in the mitochondrial respiratory chain (MRC) can lead to combined MRC dysfunctions (COXPDs) with heterogenous genotypes and clinical features. We report a patient carrying heterozygous variants in the TUFM gene who presented with clinical features compatible with COXPD4 and radiological findings mimicking multiple sclerosis (MS).
A 37-year-old French Canadian woman was investigated for recent onset of gait and balance problems. Her previous medical history included recurrent episodes of hyperventilation associated with lactic acidosis during infections, asymptomatic Wolff-Parkinson-White syndrome, and nonprogressive sensorineural deafness.
Neurological examinations revealed fine bilateral nystagmus, facial weakness, hypertonia, hyperreflexia, dysdiadochokinesia, dysmetria, and ataxic gait. Brain magnetic resonance imaging (MRI) showed multifocal white matter abnormalities in cerebral white matter as well as cerebellar hemispheres, brainstem, and middle cerebellar peduncles, some of which mimicked MS. Analysis of native-state oxidative phosphorylation showed a combined decrease in CI/CII, CIV/CII, and CVI/CII. Exome sequencing detected two heterozygous TUFM gene variants. Little clinical progression was noted over a 5-year follow-up. Brain MRI remained unchanged.
Our report broadens the phenotypic and radiological spectrum of TUFM-related disorders by adding milder, later onset forms to the previously known early onset, severe presentations. The presence of multifocal white matter abnormalities can be misinterpreted as due to acquired demyelinating diseases, and thus TUFM-related disorders should be added to the list of mitochondrial MS mimickers.
线粒体呼吸链（MRC）缺陷可导致具有异质基因型和临床特征的复合 MRC 功能障碍（COXPDs）。我们报告了一名携带 TUFM 基因突变的杂合子患者，其临床表现与 COXPD4 一致，影像学表现类似于多发性硬化症（MS）。
一名 37 岁的法裔加拿大女性因步态和平衡问题就诊。她的既往病史包括感染期间反复发作的伴乳酸酸中毒的过度通气、无症状的 Wolff-Parkinson-White 综合征和进行性感觉神经性耳聋。
神经系统检查发现双侧细小眼球震颤、面部无力、张力亢进、反射亢进、运动失调、运动幅度不准和共济失调步态。脑磁共振成像（MRI）显示大脑白质、小脑半球、脑干和中脑小脑脚多发性白质异常，部分类似于 MS。天然态氧化磷酸化分析显示 CI/CII、CIV/CII 和 CVI/CII 联合降低。外显子组测序发现两个 TUFM 基因突变的杂合子。5 年随访中未见明显临床进展。脑 MRI 保持不变。
我们的报告通过将先前已知的早发性、严重表现添加到轻度、晚发性形式，拓宽了与 TUFM 相关疾病的表型和影像学谱。多灶性白质异常的存在可能被误诊为获得性脱髓鞘疾病，因此 TUFM 相关疾病应添加到线粒体 MS 模拟物列表中。
