Objective: To report the first case of a patient with GEMIN5 and GYG-1 genes mutations who presented with features of both SCA and myopathy.

Background: Spinocerebellar ataxia (SCA) is a group of autosomal dominant progressive neurodegenerative diseases related to cerebellar involvement characterized by unsteadiness, lack of coordination and dysarthria. GEMIN5 is a RNA-binding protein, part of survival motor assembly neuron (SMN) complex, responsible for the recognition, delivery of snRNPs and the building blocks of spliceosomes. GEMIN5 mutations impairs subcellular distribution, stability and expression of this protein, thus loss-of-function. Children present with cerebellar syndrome, ataxia, tremor, and hypotonia. Adult late onset disease manifests as ataxia -present in every patient  while still ambulatory- and motor neuron disease. Furthermore, GYG-1 translates major enzymes involved in the formation of glycogen branching, expressed in muscle and other tissues. Mutations have been implicated in polyglucosan body myopathy type 2, resulting in glycogen storage disease XV (GSD XV) in striated muscle tissue. GSD XV presents as a slowly progressive weakness involving limb-girdle muscles leading to inability to raise arms and walk unassisted.

Method: A 68-year-old Hispanic male presented to the clinic with past medical history of dysarthria, ataxia, upper and lower limbs weakness, involuntary movements while sleeping resembling NREM movement disorder, retina detachment, cataracts and history of multiple direct relatives with similar symptoms. Physical examination showed bradypsychia, bradylalia, asymmetrical facies, optic disc swelling, distal tremor, trunk dystonia, hyperreflexia, bilateral Hoffman’s, left Marinescu’s, cogwheel rigidity and freeze in upper and lower limbs, Romberg’s and gait ataxia with focal left hand dystonia. MoCA Test was 20/30. Labs showed B12 deficiency, hyperhomocysteinemia, CRP, SR, ANA ENA ANCA where all negative. Whole-exome sequencing showed GEMIN5 and GYG-1 genes mutation. MRI imaging showed decreased  intensity in the putamen.

Results: Patient received treatment with dopamine and GABA agonists, but continued worsening over time. Currently he is under a progressive prognosis.

Conclusion: This is the first case to present with a non classified Spinocerebellar Ataxia plus myopathy phenotype syndrome due to GEMIN5 and GYG-1 genes mutations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/non-classified-sca-like-presentation-of-gemin5-gyg-1-mutation-case-report/