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Spastic paraplegia type 46: novel and recurrent GBA2 gene variants in a compound heterozygous Italian patient with spastic ataxia phenotype

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Abstract

Introduction

Spastic paraplegia type 46 (SPG46) is a rare autosomal recessive hereditary spastic paraplegia, caused by mutations in the non-lysosomal glucosylceramidase β2 (GBA2) gene. Worldwide, approximately twenty SPG46 families have been identified so far.

Case report

We describe a compound heterozygous Italian patient carrying a novel (p.Arg879Gln) and a recurrent (p.Arg399 *) GBA2 gene variant. The patient presented unsteady gait at age 2, and progressively manifested spastic-ataxia, scoliosis, mild intellectual decline, and bilateral cataract.

Discussion

Clinical manifestations associated with GBA2 gene variants encompass a spectrum of overlapping phenotypes including cerebellar ataxia, spastic paraplegia, and Marinesco-Sjogren-like syndrome. We review previously reported cases of SPG46 and discuss possible genetic differential diagnosis.

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Fig. 1

Data availability

Detailed genetic and clinical data are available upon request.

Code availability

Not applicable.

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Acknowledgements

We wish to thank you the participant patient and her family. The authors of this publication are members of the European Reference network for Rare Neurological Diseases- Project ID No.739510.

Funding

This work was partly supported by grant CP 20/2018 (Care4NeuroRare) from Fondazione Regionale per la Ricerca Biomedica (FRRB) to F.T.

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Authors and Affiliations

  1. Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133, Milan, Italy

    Marta Gatti, Stefania Magri, Daniela Di Bella, Elisa Sarto, Franco Taroni, Caterina Mariotti & Lorenzo Nanetti

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  1. Marta Gatti
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  2. Stefania Magri
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  3. Daniela Di Bella
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  4. Elisa Sarto
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  5. Franco Taroni
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  6. Caterina Mariotti
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  7. Lorenzo Nanetti
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Correspondence to Caterina Mariotti.

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Written informed consent was obtained from the patient, according to hospital IRB approved procedures for genetic analyses.

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Gatti, M., Magri, S., Di Bella, D. et al. Spastic paraplegia type 46: novel and recurrent GBA2 gene variants in a compound heterozygous Italian patient with spastic ataxia phenotype. Neurol Sci 42, 4741–4745 (2021). https://doi.org/10.1007/s10072-021-05463-0

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