Characterization of cognitive impairment in adult polyglucosan body disease

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.

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

PRISMA flow diagram of study selection

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