Adult polyglucosan body disease: Case description of an expanding genetic and clinical syndrome

Klein, Christopher J.; Boes, Christopher J.; Chapin, J. E.; Lynch, Christopher D.; Campeau, Norbert G.; Dyck, Peter J.

doi:10.1002/mus.10520

Cited by 53 publications

(60 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A diagnosis that should also be considered is adult-onset polyglucosan body disease, characterized clinically by cognitive impairment, pyramidal involvement, sensory-motor polyneuropathy, sphincter dysfunction, sometimes with cerebellar ataxia and extrapyramidal signs, and neuroradiologically by white matter changes and atrophy of medulla oblongata and spinal cord (Klein et al, 2004).…”

Section: Neuroradiologic Aspectsmentioning

confidence: 99%

Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature

Pareyson¹,

Fancellu²,

Mariotti³

et al. 2008

Brain

163

151

View full text Add to dashboard Cite

Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem^spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4 -year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading.The most frequent symptoms were related to bulbar dysfunctionçwith dysarthria, dysphagia, dysphonia (seven patients)ç, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs.When present, palatal myoclonus is strongly suggestive. Pyramidal involvement, cerebellar ataxia and urinary disturbances are common. Less frequent findings include sleep disorders and dysautonomia. Fluctuations may occur. The course is variable, usually slowly progressive and less severe than the AD forms with earlier onset. AOAD is more common than previously thought and might even be the most common form of AD. The diagnosis is strongly suggested by MRI and confirmed by GFAP gene analysis.Keywords: Alexander disease; GFAP; brainstem diseases; medulla oblongata atrophy; palatal myoclonus Abbreviations: AD = Alexander disease; AOAD = adult-onset AD; FLAIR = fluid-attenuated inversion recovery; GFAP = glial fibrillary acidic protein

show abstract

Section: Neuroradiologic Aspectsmentioning

confidence: 99%

Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature

Pareyson¹,

Fancellu²,

Mariotti³

et al. 2008

Brain

163

151

View full text Add to dashboard Cite

show abstract

“…33 In order to explain PB deposition in these two cases the occurrence of posttranscriptional or posttranslational defects and the influence of environmental factors have been suggested. 22,33 This hypothesis may apply to other cases with "atypical" GBE insufficiency.…”

Section: Discussionmentioning

confidence: 92%

“…21,30,32 Brain MRI findings showed severe alterations of the hemispheric WM that, although described in APBD, are not distinctive compared to those seen in the leukodystrophies. 5,22,23,33 In considering our 1 H-MRSI findings, a reduction of NAA/Cr should be interpreted, as in other neurological disorders, as an index of neuro-axonal damage or loss due to the decrease of NAA. 7,17 The presence of widespread neuro-axonal damage in postmortem APBD brains seems to give further support to this hypothesis.…”

Section: Discussionmentioning

confidence: 98%

“…The first case was a non-Jewish patient with complete GBE deficiency and no mutation in the GBE1 gene. 22 The second case was a patient of Ashkenazi descent with partial GBE deficiency (in the heterozygous range) and the Tyr329Ser mutation in heterozygosity. At variance with other carriers, this patient displayed the full-blown disease.…”

Section: Discussionmentioning

confidence: 99%

“…10,21,23,33 A few magnetic resonance imaging (MRI) studies have shown nonspecific, leukodystrophy-like changes in cerebral white matter (WM), along with brain and spinal cord atrophy. 5,22,23,33 Most cases are apparently sporadic but a few familial clusterings involving siblings have been reported. 6,12,23,30 The diagnosis of APBD is generally made by exclusion of other clinical-pathological entities, and most cases have been defined by examination of autopsy material.…”

Section: Accepted 17 September 2007mentioning

confidence: 98%

See 2 more Smart Citations

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

et al. 2008

View full text Add to dashboard Cite

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.

show abstract

Branching Enzyme Deficiency

et al. 2014

View full text Add to dashboard Cite

Adult polyglucosan body disease: Case description of an expanding genetic and clinical syndrome

Cited by 53 publications

References 16 publications

Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature

Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature

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

Branching Enzyme Deficiency

Contact Info

Product

Resources

About