Abstract
Background: Type-III (adult/chronic) GM1 gangliosidosis is an uncommon, late-onset lysosomal disorder that frequently presents as a complex movement disorder.
Methods: In this retrospective case series, clinical details, neuroimaging, electrophysiology, and genetics were extracted from standardized records and videos.
Results: Eight patients were identified with median age at symptom onset of 6 years (range 3–18), and age at presentation of 23 years (12–27). All exhibited generalized dystonia with early, conspicuous oro-mandibular-cranio-cervical involvement; dysarthria was universal, parkinsonism occurred in two, and corticospinal signs in six. Ocular motor abnormalities were frequent; kyphoscoliosis was common. Where performed, nerve conduction studies, electroencephalography, evoked potentials, and abdominal ultrasound were unremarkable. MRI consistently demonstrated bilateral posterior putaminal T2/FLAIR change and the pathognomonic pallidal SWI “wishbone” pattern. All patients harboured biallelic GLB1 variants: seven were compound heterozygous and one was homozygous. The recurrent variant c.1325G>A;p.Arg442Gln was present in seven patients. One novel variant (c.1022G>T;p.Gly341Val) was identified. Symptomatic therapies yielded variable, generally modest benefits over available follow-up.
Discussion: A prominent oromandibular–cranio–cervical dystonia, posterior putaminal atrophy, and hyperintensity, with a SWI “wishbone” sign, strongly point to Type-III GM1 gangliosidosis. Recognizing this clinico-radiologic–genetic constellation can streamline targeted testing and counselling.