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. 2022 Jun;269(6):2854-2861.
doi: 10.1007/s00415-022-10960-z. Epub 2022 Jan 8.

Characterization of cognitive impairment in adult polyglucosan body disease

Paul Theo Zebhauser  1 , Isabell Cordts  2 , Holger Hengel  3 , Bernhard Haslinger  2 , Paul Lingor  2 , Hasan Orhan Akman  4 , Tobias B Haack  3   5 , Marcus Deschauer  2
Affiliations

Characterization of cognitive impairment in adult polyglucosan body disease

Paul Theo Zebhauser et al. J Neurol. 2022 Jun.

Abstract

Adult polyglucosan body disease (APBD) is a rare but probably underdiagnosed autosomal recessive neurodegenerative disorder due to pathogenic variants in GBE1. The phenotype is characterized by neurogenic bladder dysfunction, spastic paraplegia, and axonal neuropathy. Additionally, cognitive symptoms and dementia have been reported in APBD but have not been studied systematically. Using exome sequencing, we identified two previously unreported bi-allelic missense GBE1 variants in a patient with severe memory impairment along with the typical non-cognitive symptoms. We were able to confirm a reduction of GBE1 activity in blood lymphocytes. To characterize the neuropsychological profile of patients suffering from APBD, we conducted a systematic review of cognitive impairment in this rare disease. Analysis of 24 cases and case series (in total 58 patients) showed that executive deficits and memory impairment are the most common cognitive symptoms in APBD.

Keywords: Adult polyglucosan body disease; Cognitive impairment; Dementia; GBE1; Glycogen-branching enzyme.

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Conflict of interest statement

The authors report no conflicts of interest in regard to this work.

Figures

Fig. 1
Fig. 1
Cranial and spinal magnetic resonance imaging sections and MRI sequence from left to right—axial FLAIR, coronal FLAIR, and sagittal T2
Fig. 2
Fig. 2
PRISMA flow diagram of study selection
Fig. 3
Fig. 3
Proportional Venn diagrams of reported cognitive impairment in studies of patients with APBD split by method of evaluation. Only studies from Table 2 which reported cognitive impairments in specific domains (attention, executive functioning, memory) are included
See this image and copyright information in PMC

References

    1. Souza PVS, et al. GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes. J Inherit Metab Dis. 2021;44(3):534–543. doi: 10.1002/jimd.12325. - DOI - PubMed
    1. Mochel F, et al. Adult polyglucosan body disease: natural history and key magnetic resonance imaging findings. Ann Neurol. 2012;72(3):433–441. doi: 10.1002/ana.23598. - DOI - PMC - PubMed
    1. Hellmann MA, et al. Frequent misdiagnosis of adult polyglucosan body disease. J Neurol. 2015;262(10):2346–2351. doi: 10.1007/s00415-015-7859-4. - DOI - PubMed
    1. Boulan-Predseil P, Vital A, Brochet B, Darriet D, Henry P, Vital C. Dementia of frontal lobe type due to adult polyglucosan body disease. J Neurol. 1995 doi: 10.1007/BF00867422. - DOI - PubMed
    1. Farmer JG, Crain BJ, Harris BT, Turner RS. Coexisting adult polyglucosan body disease with frontotemporal lobar degeneration with transactivation response DNA-binding protein-43 (TDP-43)-positive neuronal inclusions. Neurocase. 2013;19(1):67–75. doi: 10.1080/13554794.2011.654217. - DOI - PMC - PubMed

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Supplementary concepts