Adult polyglucosan body disease: Proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene

Abstract

Adult polyglucosan body disease (APBD) is characterized by the accumulation of insoluble glucose polymers within the central and peripheral nervous systems. A common missense mutation in the glycogen branching enzyme (GBE1) gene has been identified in Ashkenazi patients with APBD. We report on a non-Jewish patient with APBD on whom we performed proton magnetic resonance spectroscopic imaging of the brain. GBE activity in fibroblasts was markedly reduced, and a novel heterozygous mutation was identified in the GBE1 gene. Our findings widen the spectrum of APBD genotypes, underline the importance of performing GBE analysis in all APBD patients, and suggest that brain white matter degeneration in APBD may result from tissue damage involving axons and myelin.

Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review

“…Genotypephenotype correlations remain unclear yet are beginning to emerge. A review of previously reported patients suggests that individuals with the congenital presentation of GSD IV tend to have 2 null mutations, likely resulting in completely the mutations identified in the present case are indicated by an asterisk [33][34][35][36][37]. absent GBE enzyme activity; individuals with the classic hepatic form of GSD IV tend to be compound heterozygotes for a null and missense mutation, and APBD is typically the result of homozygous or compound heterozygous missense mutations (Table 1).…”

Acute but transient neurological deterioration revealing adult polyglucosan body disease

“…Most of previous reports exhibited intra-axonal PBs in sural nerve biopsy [2,4,[6][7][8]. All these patients had a peripheral neuropathy confirmed by nerve conduction studies and, in most cases, muscle biopsy showed only features of chronic denervation without PBs.…”

“…However, in a significant number of patients, only one heterozygous mutation has been found despite similar residual enzymatic activity than patients with two identified mutations [3,4]. In fewer cases, no mutation has been found in GBE1 [5], suggesting a genetic heterogeneity.…”

Adult polyglucosan body disease

“…Medullary and spinal cord atrophy are early invariable MRI findings, whereas cortical atrophy and a thin corpus callosum are seen later. MRS of the involved cerebral white matter may shows reduced NAA/Cr ratio and elevated lactate signal, reflecting the underlying processes involved in axonal loss and demyelination [14].…”

“…The p.Y329S mutation is found in 76% of patients, particularly of Ashkenazi Jewish ancestry [9]. Despite apparent autosomal recessive inheritance [6, 7], a proportion of APBD patients are p.Y329S heterozygotes [9,14], yet are clinically and biochemically indistinguishable from homozygotes, suggesting additional genetic or environmental factors. Epidemiologically, one study showed this mutation to occur at a frequency of 1:34.5 in Ashkenazi Jewish population [20].…”