Advertisement

pp 1-6 | Cite as

Glycogen Storage Disease Type IV: A Rare Cause for Neuromuscular Disorders or Often Missed?

  • Imre F. Schene
  • Christoph G. Korenke
  • Hidde H. Huidekoper
  • Ludo van der Pol
  • Dennis Dooijes
  • Johannes M. P. J. Breur
  • Saskia Biskup
  • Sabine A. Fuchs
  • Gepke Visser
Research Report
Part of the JIMD Reports book series

Abstract

Advancements in genetic testing now allow early identification of previously unresolved neuromuscular phenotypes. To illustrate this, we here present diagnoses of glycogen storage disease IV (GSD IV) in two patients with hypotonia and delayed development of gross motor skills. Patient 1 was diagnosed with congenital myopathy based on a muscle biopsy at the age of 6 years. The genetic cause of his disorder (two compound heterozygous missense mutations in GBE1 (c.[760A>G] p.[Thr254Ala] and c.[1063C>T] p.[Arg355Cys])), however, was only identified at the age of 17, after panel sequencing of 314 genes associated with neuromuscular disorders. Thanks to the availability of next-generation sequencing, patient 2 was diagnosed before the age of 2 with two compound heterozygous mutations in GBE1 (c.[691+2T>C] (splice donor variant) and the same c.[760A>G] p.[Thr254Ala] mutation as patient 1). GSD IV is an autosomal recessive metabolic disorder with a broad and expanding clinical spectrum, which hampers targeted diagnostics. The current cases illustrate the value of novel genetic testing for rare genetic disorders with neuromuscular phenotypes, especially in case of clinical heterogeneity. We argue that genetic testing by gene panels or whole exome sequencing should be considered early in the diagnostic procedure of unresolved neuromuscular disorders.

Keywords

Congenital myopathy Gene panel Genetic testing Glycogen storage disease IV Hypotonia 

Supplementary material

8904_2018_148_MOESM1_ESM.docx (229 kb)
Supplementary Material ■ (DOCX 228 kb)

References

  1. Akalin F, Alper G, Oztunç F, Kotiloğlu E, Turan S (2000) A case of glycogen storage disease type II with double aortic arch. Acta Paediatr 89(7):884–886Google Scholar
  2. Burrow TA, Hopkin RJ, Bove KE et al (2006) Non-lethal congenital hypotonia due to glycogen storage disease type IV. Am J Med Genet A 140:878–882Google Scholar
  3. Choi M, Scholl UI, Ji W (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A 106(45):19096–19101Google Scholar
  4. Colombo I, Pagliarani S, Testolin S et al (2015) Adult polyglucosan body disease: clinical and histological heterogeneity of a large Italian family. Neuromuscul Disord 25:423–428Google Scholar
  5. Fernandez C, Halbert C, De Paula AM et al (2010) Non-lethal neonatal neuromuscular variant of glycogenosis type IV with novel GBE1 mutations. Muscle Nerve 41:269–271Google Scholar
  6. Klein CJ (2013) Adult polyglucosan body disease. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJ et al (eds) GeneReviews. University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/NBK5300/. Retrieved 1 Dec 2017Google Scholar
  7. Lee YC, Chang CJ, Bali D, Chen YT, Yan YT (2011) Glycogen-branching enzyme deficiency leads to abnormal cardiac development: novel insights into glycogen storage disease IV. Hum Mol Genet 20(3):455–456Google Scholar
  8. Li S, Chen C, Goldstein J et al (2010) Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder. J Inherit Metab Dis 33(3):S83–S90Google Scholar
  9. Magoulas PL, El-Hattab AW (2013) Glycogen storage disease type IV. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJ et al (eds) GeneReviews. University of Washington, Seattle. https://www.ncbi.nlm.nih.gov/books/NBK115333/. Retrieved 1 Dec 2017Google Scholar
  10. Magoulas PL, El-Hattab AW, Angshumoy R, Bali DS, Finegold MJ, Craigen WJ (2012) Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review. Hum Pathol 43:943–951Google Scholar
  11. Moses SW, Parvari R (2002) The variable presentations of glycogen storage disease type IV. Curr Mol Med 2(2):177–188Google Scholar
  12. Ravenscroft G, Thompson EM, Todd EJ et al (2013) Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. Neuromuscul Disord 23:165–169Google Scholar
  13. Reid ES, Papandreou A, Drury S et al (2016) Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes. Brain 139:2844–2854Google Scholar
  14. Said SM, Murphree MI, Mounajjed T, El-Youssef M, Zhang L (2016) A novel GBE1 gene variant in a child with glycogen storage disease type IV. Hum Pathol 54:152–156Google Scholar
  15. Slepov AK, Chumakov LF (1997) Co-occurrence of double aortic arch with mucopolysaccharidosis in an infant. Klin Khir 7–8:105Google Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Imre F. Schene
    • 1
  • Christoph G. Korenke
    • 2
  • Hidde H. Huidekoper
    • 3
  • Ludo van der Pol
    • 4
  • Dennis Dooijes
    • 5
  • Johannes M. P. J. Breur
    • 6
  • Saskia Biskup
    • 7
  • Sabine A. Fuchs
    • 1
  • Gepke Visser
    • 1
  1. 1.Department of Metabolic DiseasesWilhelmina Children’s Hospital, University Medical Centre UtrechtUtrechtThe Netherlands
  2. 2.Department of NeuropediatricsChildren’s Hospital Klinikum OldenburgOldenburgGermany
  3. 3.Department of Pediatrics, Center for Lysosomal and Metabolic DiseasesErasmus Medical CenterRotterdamThe Netherlands
  4. 4.Department of NeurologyUniversity Medical Centre UtrechtUtrechtThe Netherlands
  5. 5.Department of Medical GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
  6. 6.Department of Pediatric CardiologyWilhelmina Children’s Hospital, University Medical Centre UtrechtUtrechtThe Netherlands
  7. 7.CeGaT GmbH and Praxis für Humangenetik TübingenTübingenGermany

Personalised recommendations