# Clinical, Radiological, and Genetic Profiles of Eight Patients with Combined Dystonic Manifestation of Type-III GM1 Gangliosidosis: A Video Case Series from India

## TL;DR

This study presents eight Indian patients with a rare adult-onset GM1 gangliosidosis, highlighting key clinical, radiological, and genetic features to aid in diagnosis.

## Contribution

The paper provides a detailed video case series of Type-III GM1 gangliosidosis with a focus on distinctive clinical and radiological markers in an Indian population.

## Key findings

- All eight patients showed generalized dystonia with early oro-mandibular-cranio-cervical involvement and MRI features like the 'wishbone' sign.
- Biallelic GLB1 variants were identified in all patients, including a novel variant c.1022G>T;p.Gly341Val.
- Symptomatic treatments provided only modest benefits, emphasizing the need for early diagnosis and targeted management.

## Abstract

Type-III (adult/chronic) GM1 gangliosidosis is an uncommon, late-onset lysosomal disorder that frequently presents as a complex movement disorder.

In this retrospective case series, clinical details, neuroimaging, electrophysiology, and genetics were extracted from standardized records and videos.

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.

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.