Neuroimaging Spectrum of GM1 Gangliosidosis with Description of Novel Imaging Signs

GM1 gangliosidosis is a rare lysosomal storage disorder caused by pathogenic variants in the GLB1 gene, leading to deficient β-galactosidase activity and accumulation of gangliosides. This multi-institutional retrospective study aims to systematically characterize neuroimaging features across all clinical subtypes of GM1 gangliosidosis.

Patients were retrospectively identified from 4 centers based on confirmed GLB1 variants or β-galactosidase deficiency. Imaging acquired post gene therapy or with poor quality was excluded. Clinical subtypes were classified by age of onset. A total of 35 brain MRIs and 3 CTs from 24 patients (aged 0-19 years) were reviewed. Imaging was assessed for white matter patterns, deep gray nuclei signal changes, atrophy, and the presence of occipitomastoid suture hypertrophy.

The cohort included patients with infantile- (13), late-infantile- (6), juvenile- (4), and adult-onset (1). White matter abnormalities were present in all but one infantile/late-infantile patient and absent in juvenile/adult-onset subtypes. Patients with infantile-onset predominantly showed hypomyelination with the posterior limb of the internal capsule sparing. Late-infantile subtypes demonstrated a spectrum from mixed to nonhypomyelinating patterns, including periventricular and deep white matter involvement with sparing of subcortical regions. Internal hypertrophy of the occipitomastoid sutures was seen in more than one-half of the infantile and late-infantile-onset subtypes. One patient in the infantile cohort showed linear subcortical and basal ganglia calcifications. Thalamic T2 hypointensity with anterior and lateral nuclear group predilection was a consistent feature across all subtypes, progressing in early-onset groups. Juvenile and adult cases showed dorsal putaminal T2 hyperintensity and globus pallidus T2 hypointensity, with the latter corresponding to mineralization on SWI. Progressive cerebral and cerebellar atrophy was observed in all subtypes with available follow-up imaging.

Distinct imaging patterns are evident across GM1 gangliosidosis subtypes: leukodystrophy dominates in early-onset forms, while juvenile and adult forms are characterized by globus pallidus mineralization and dorsal putaminal atrophy. Thalamic T2 hypointensity is consistent across all subtypes, with predilection for the anterior and lateral nuclear groups. Internal hypertrophy of the occipitomastoid sutures, previously undescribed in GM1 gangliosidosis, is a common feature of early-onset cases.