Graziola Federica, Danti Federica Rachele, Penzo Martina, Spagarino Antonio, Minacapilli Eleonora, Moscatelli Marco, Zibordi Federica, Mariotti Caterina, Zorzi Giovanna
Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Department of Biomedical and Clinical Sciences, Postgraduate School of Child Neuropsychiatry, University of Milan, Milan, Italy.
Front Neurol. 2025 Aug 20;16:1626275. doi: 10.3389/fneur.2025.1626275. eCollection 2025.
Pediatric Huntington's disease (PHD), a rare and severe form of juvenile-onset Huntington's disease (JOHD), is associated with highly expanded CAG repeats in the gene and a rapidly progressive neurodegenerative course. Recent studies have suggested that glucose metabolism may be impaired in PHD due to reduced expression of glucose transporters in the brain, resembling aspects of GLUT1 Deficiency Syndrome (GLUT1DS).
We investigated glucose metabolism in two pediatric patients with genetically confirmed PHD (CAG repeats: 76 and 79) referred to our tertiary care center. Clinical, neuroimaging, and neuropsychological data were collected alongside metabolic assessments, including cerebrospinal fluid (CSF) and plasma glucose and lactate levels, CSF-to-serum glucose ratio, and red blood cell GLUT1 expression using the METAglut1 test. 18F-FDG PET imaging and brain MRI were performed to assess cerebral metabolism and structural changes.
Both patients exhibited progressive motor and cognitive decline with dystonia-parkinsonian features, learning disabilities, and behavioral disturbances. Brain MRI showed caudate and putaminal atrophy, while PET imaging demonstrated severely reduced glucose uptake in the basal ganglia. CSF/plasma glucose ratios were within or near the lower end of the normal range (0.51 and 0.6), and GLUT1 expression in red blood cells was within normal limits. No significant biochemical alterations consistent with GLUT1DS were detected.
Our findings confirm localized cerebral hypometabolism in the basal ganglia of PHD patients, consistent with previous neuropathological reports. However, systemic biochemical indicators of glucose transport deficiency, including erythrocyte GLUT1 function and CSF glucose, were not significantly altered. While glucose dysregulation appears to be a feature of PHD brain pathology, our results do not support the use of metabolic interventions such as the ketogenic diet in the absence of confirmed GLUT1 dysfunction. Further studies in larger cohorts are warranted to better characterize the metabolic profile of PHD and guide therapeutic strategies.
小儿亨廷顿舞蹈病（PHD）是青少年型亨廷顿舞蹈病（JOHD）的一种罕见且严重的形式，与该基因中高度扩增的CAG重复序列以及快速进展的神经退行性病程相关。最近的研究表明，由于大脑中葡萄糖转运蛋白表达降低，PHD患者可能存在葡萄糖代谢受损，类似于葡萄糖转运体1缺乏综合征（GLUT1DS）的某些方面。
我们对两名转诊至我们三级医疗中心、基因检测确诊为PHD（CAG重复序列分别为76和79）的儿科患者的葡萄糖代谢情况进行了研究。收集了临床、神经影像学和神经心理学数据以及代谢评估结果，包括脑脊液（CSF）和血浆葡萄糖及乳酸水平、脑脊液与血清葡萄糖比值，以及使用METAglut1检测法检测红细胞GLUT1表达。进行了18F - FDG PET成像和脑部MRI以评估脑代谢和结构变化。
两名患者均表现出进行性运动和认知功能下降，伴有肌张力障碍 - 帕金森样特征、学习障碍和行为紊乱。脑部MRI显示尾状核和壳核萎缩，而PET成像显示基底神经节葡萄糖摄取严重减少。脑脊液/血浆葡萄糖比值在正常范围的下限或接近下限（分别为0.51和0.6），红细胞中GLUT1表达在正常范围内。未检测到与GLUT1DS一致的明显生化改变。
我们的研究结果证实了PHD患者基底神经节存在局部脑代谢减退，与先前的神经病理学报告一致。然而，包括红细胞GLUT1功能和脑脊液葡萄糖在内的葡萄糖转运缺乏的全身生化指标并未显著改变。虽然葡萄糖调节异常似乎是PHD脑病理学的一个特征，但在未确认GLUT1功能障碍的情况下，我们的结果不支持使用生酮饮食等代谢干预措施。有必要对更大的队列进行进一步研究，以更好地描述PHD的代谢特征并指导治疗策略。
