Adult polyglucosan body disease—an atypical compound heterozygous with a novel GBE1 mutation

Abstract

Introduction

Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder starting after 40 years old, spastic paraparesis and peripheral neuropathy. It is mainly resultant from the GBE1 homozygous p.Tyr329Ser (c.986A>C) mutation, especially in Ashkenazi-Jewish patients, although some cases of compound heterozygous have been reported. A genotype-phenotype correlation is not established, but atypical phenotypes have been described mainly in non-p.Tyr329Ser pathogenic variants.

Case report

We describe an atypical case in a 62-year-old Portuguese woman, presenting the typical clinical triad of APBD plus prominent autonomic dysfunction, suggested by orthostatic hypotension and thermoregulatory dysfunction; she has compound heterozygous GBE1 mutations, namely, p.Asn541Asp (c.1621A>G) and p.Arg515Gly (c.1543C>G), the last one not yet reported in literature and whose pathogenicity was suggested by bioinformatics analysis and confirmed by sural nerve biopsy that showed intra-axonal polyglucosan bodies.

Discussion

Besides the report of a novel GBE1 mutation, this case also expands the phenotypic spectrum of this disorder, reinforcing autonomic dysfunction as a possible and prominent manifestation of APBD, mimicking autosomal dominant leukodystrophy with autonomic disease in some way. Therefore, we questioned a possible relationship between this genotype and the phenotype marked by dysautonomia. Additionally, we review previously reported cases of APBD in non-homozygous p.Tyr329Ser patients with atypical phenotypes.

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References

  1. 1.

    Klein CJ (2009) (Updated 2013 Dec 19) Adult polyglucosan body disease. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5300/. Accessed 19 Jan 2020

  2. 2.

    Ziemssen F, Sindern E, Schröder JM, Shin YS, Zange J, Kilimann MW et al (2000) Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease. Ann Neurol 47:536–540

    CAS  Article  Google Scholar 

  3. 3.

    Colombo I, Pagliarani S, Testolin S, Salsano E, Napoli LM, Bordoni A, Salani S, D'Adda E, Morandi L, Farina L, Magri F, Riva M, Prelle A, Sciacco M, Comi GP, Moggio M (2015) Adult polyglucosan body disease: clinical and histological heterogeneity of a large Italian family. Neuromuscul Disord 25:423–428. https://doi.org/10.1016/j.nmd.2015.01.015

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Paradas C, Akman HO, Ionete C, Lau H, Riskind PN, Jones DE, Smith TW, Hirano M, DiMauro S (2014) Branching enzyme deficiency: expanding the clinical spectrum. JAMA Neurol 71:41–47. https://doi.org/10.1001/jamaneurol.2013.4888

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Naddaf E, Kassardjian CD, Kurt YG, Akman HO, Windebank AJ (2016) Adult polyglucosan body disease presenting as a unilateral progressive plexopathy. Muscle Nerve 53:976–981. https://doi.org/10.1002/mus.25041

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Harigaya Y, Matsukawa T, Fujita Y, Mizushima K, Ishiura H, Mitsui J, Morishita S, Shoji M, Ikeda Y, Tsuji S (2017) Novel GBE1 mutation in a Japanese family with adult polyglucosan body disease. Neurol Genet 3:e138. https://doi.org/10.1212/NXG.0000000000000138

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Sampaolo S, Esposito T, Gianfrancesco F, Napolitano F, Lombardi L, Lucà R, Roperto F, di Iorio G (2015) A novel GBE1 mutation and features of polyglucosan bodies autophagy in adult polyglucosan body disease. Neuromuscul Disord 25:247–252. https://doi.org/10.1016/j.nmd.2014.11.006

    Article  PubMed  Google Scholar 

  8. 8.

    Sindern E, Ziemssen F, Ziemssen T, Podskarbi T, Shin Y, Brasch F, Muller KM, Schroder JM, Malin JP, Vorgerd M (2003) Adult polyglucosan body disease: a postmortem correlation study. Neurology 61:263–265. https://doi.org/10.1212/01.wnl.0000073144.96680.cb

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Mochel F, Schiffmann R, Steenweg ME, Akman HO, Wallace M, Sedel F, Laforêt P, Levy R, Powers JM, Demeret S, Maisonobe T, Froissart R, da Nobrega BB, Fogel BL, Natowicz MR, Lubetzki C, Durr A, Brice A, Rosenmann H, Barash V, Kakhlon O, Gomori JM, van der Knaap MS, Lossos A (2012) Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings. Ann Neurol 72:433–441. https://doi.org/10.1002/ana.23598

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Finnsson J, Sundblom J, Dahl N, Melberg A, Raininko R (2015) LMNB1-related autosomal-dominant leukodystrophy: clinical and radiological course. Ann Neurol 78:412–425. https://doi.org/10.1002/ana.24452

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Andreia Carvalho.

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Carvalho, A., Nunes, J., Taipa, R. et al. Adult polyglucosan body disease—an atypical compound heterozygous with a novel GBE1 mutation. Neurol Sci (2021). https://doi.org/10.1007/s10072-021-05096-3

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Keywords

  • Adult polyglucosan body disease
  • Autonomic dysfunction
  • Leukodystrophy
  • Neurogenic bladder
  • Peripheral neuropathy
  • Spastic paraparesis