Wortmann Saskia B, van Hasselt Peter M, Barić Ivo, Burlina Alberto, Darin Niklas, Hörster Friederike, Coker Mahmut, Ucar Sema Kalkan, Krumina Zita, Naess Karin, Ngu Lock H, Pronicka Ewa, Riordan Gilian, Santer Rene, Wassmer Evangeline, Zschocke Johannes, Schiff Manuel, de Meirleir Linda, Alowain Mohammed A, Smeitink Jan A M, Morava Eva, Kozicz Tamas, Wevers Ron A, Wolf Nicole I, Willemsen Michel A
Department of Pediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
Department of Metabolic Diseases, Wilhelmina Children's Hospital Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Neuropediatrics. 2015 Apr;46(2):98-103. doi: 10.1055/s-0034-1399755. Epub 2015 Feb 2.
Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.
儿童运动障碍仍然是一个诊断难题，因为许多患者仍未得到（基因）诊断。磁共振成像（MRI）模式识别有助于诊断。MEGDEL综合征（3-甲基戊二酸尿症、耳聋、脑病、类 Leigh 综合征，MIM #614739）是一种临床和生化特征高度独特的肌张力障碍性耳聋综合征，伴有3-甲基戊二酸尿症、严重发育迟缓及进行性痉挛。已发现该综合征由 SERAC1 基因突变所致，SERAC1 编码一种对线粒体功能和细胞内胆固醇转运均至关重要的磷脂酰甘油重塑酶。基于其同质化的表型，我们推测其MRI模式也具有相应特征。我们对30例患者的43份完整MRI研究进行了系统的重新评估。所有患者均呈现出一种独特的脑部MRI模式，有五个特征性疾病阶段，累及基底神经节，尤其是壳核。在第1阶段出现苍白球T2信号改变。在第2阶段可见壳核和尾状核肿胀。背侧壳核有一个“眼”，信号无改变，在疾病的这个阶段似乎未受影响。随后它会增大，表示壳核受累进展。在特定年龄范围内，所有MEGDEL综合征患者均出现这种“眼”征，其他疾病未见报道，使其成为MEGDEL综合征的特征性表现，可据此基于MRI结果进行诊断。
