Kolstad Josephine, Zoppo Christopher, Johnston Jean M, D'Souza Precilla, Kühn Anna Luisa, Vardar Zeynep, Peker Ahmet, Hader Asma, Celik Hakki, Lewis Connor J, Lindsay Clifford, Rentiya Zubir S, Lebel Catherine, Vedantham Srinivasan, Vachha Behroze, Gray-Edwards Heather L, Acosta Maria T, Tifft Cynthia J, Shazeeb Mohammed Salman
Image Processing & Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA; McLean Hospital, Belmont, MA, USA.
Image Processing & Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Mol Genet Metab. 2025 Mar;144(3):109025. doi: 10.1016/j.ymgme.2025.109025. Epub 2025 Jan 19.
GM1 gangliosidosis is a rare lysosomal storage disorder characterized by the accumulation of GM1 gangliosides in neuronal cells, resulting in severe neurodegeneration. Currently, limited data exists on the brain volumetric changes associated with this disease. This study focuses on the late-infantile and juvenile subtypes of type II GM1 gangliosidosis, aiming to quantify brain volumetric characteristics to track disease progression.
Brain volumetric analysis was conducted on 56 MRI scans from 24 type II GM1 patients (8 late-infantile and 16 juvenile) and 19 healthy controls over multiple time points. The analysis included the use of semi-automated segmentation of the whole brain, ventricles, cerebellum, corpus callosum, thalamus, caudate, and lentiform nucleus. A generalized linear model was used to compare the volumetric measurements between the patient groups and healthy controls, accounting for age as a confounding factor.
Both late-infantile and juvenile GM1 patients exhibited significant whole-brain atrophy compared to healthy controls, even after adjusting for age. Notably, the late-infantile subtype displayed more pronounced atrophy in the cerebellum, thalamus, and corpus callosum compared to the juvenile subtype. Both late-infantile and juvenile subtypes showed significantly higher ventricular volumes and a significant reduction in all other structure volumes compared to the healthy controls. The volumetric measurements also correlated well with disease severity based on clinical metrics.
The findings underscore the distinct brain volumetrics of the late-infantile and juvenile subtypes of GM1 gangliosidosis compared to healthy controls. These quantifications can be used as reliable imaging biomarkers to track disease progression and evaluate responses to therapeutic interventions.
GM1神经节苷脂贮积症是一种罕见的溶酶体贮积病，其特征是GM1神经节苷脂在神经元细胞中蓄积，导致严重的神经退行性变。目前，关于该疾病相关脑容量变化的数据有限。本研究聚焦于II型GM1神经节苷脂贮积症的晚婴儿型和青少年型，旨在量化脑容量特征以追踪疾病进展。
对24例II型GM1患者（8例晚婴儿型和16例青少年型）和19名健康对照者的56次MRI扫描进行了多个时间点的脑容量分析。分析包括使用半自动分割全脑、脑室、小脑、胼胝体、丘脑、尾状核和豆状核。使用广义线性模型比较患者组和健康对照者之间的容量测量值，并将年龄作为混杂因素考虑在内。
与健康对照者相比，即使在调整年龄后，晚婴儿型和青少年型GM1患者均表现出明显的全脑萎缩。值得注意的是，与青少年型相比，晚婴儿型在小脑、丘脑和胼胝体中表现出更明显的萎缩。与健康对照者相比，晚婴儿型和青少年型均显示出明显更高的脑室容积，而所有其他结构容积均显著减少。基于临床指标的容量测量值也与疾病严重程度密切相关。
这些发现强调了GM1神经节苷脂贮积症的晚婴儿型和青少年型与健康对照者相比具有不同的脑容量特征。这些量化结果可作为可靠的影像学生物标志物来追踪疾病进展并评估对治疗干预的反应。
