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Genetics of Glycogen-Storage Disease Type IV Follow-up

  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Maria Descartes, MD  more...
 
Updated: Jan 08, 2016
 

Further Outpatient Care

Perform follow-up in patients with glycogen-storage disease type IV (GSD IV) to evaluate the progression of liver disease, to determine the need for additional medical and dietary management, and to assess the urgency for surgical intervention. Periodic ultrasonography of the liver to monitor the development of hepatocellular adenoma is suggested.

Perform periodic follow-up to evaluate progressive organ involvement and failure in patients with predominant nerve, muscle, and cardiac involvement.

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Deterrence/Prevention

The parents of an affected child should be provided genetic counseling regarding the autosomal recessive inheritance pattern and the 1:4 risk (25%) of an affected offspring with each pregnancy.

The parents of an affected child should be informed that analysis of the GBE1 gene by sequencing and other molecular techniques may identify the mutations in their child. Subsequently, if the mutations of an affected child are identified, then prenatal diagnostic testing may be offered for future pregnancies.

The parents of an affected child should be informed that if the mutations in an affected child are identified, genetic testing may be offered to close family members to determine carrier status for the GBE1 mutation.

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Complications

The following complications may result from the disease process and medical or surgical interventions:

  • Patients with liver cirrhosis who develop portal hypertension may develop complications of portosystemic blood shunting, including esophageal varices, encephalopathy splenomegaly, ascites, and renal dysfunction
  • Patients with progressive liver disease may develop complications related to declining hepatic functional capacity.
  • Patients with cardiomyopathy may die from progressive heart failure despite medical and surgical intervention.
  • Patients with nonprogressive liver disease have an increased risk for hepatocellular adenoma and hepatocellular carcinoma.
  • Immediate complications of liver transplantation include postoperative complications and organ rejection.
  • Long-term complications after liver transplantation include the progression of disease in other organs.
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Prognosis

The prognosis is poor in patients with the perinatal-onset and classic forms who do not undergo liver transplantation. Long-term prognosis for others, including patients with classic glycogen-storage disease type IV after transplantation, depends on the extent, severity, and progression of this multisystem disorder.

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Patient Education

Educate patients and parents about proper diet management to support liver dysfunction.

Educate patients and parents about proper evaluation and long-term medical management of complications such as cirrhosis and portal hypertension, heart failure, and neuromuscular dysfunction.

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Contributor Information and Disclosures
Author

Lynne Ierardi-Curto, MD, PhD Attending Physician, Division of Metabolism, Children's Hospital of Philadelphia

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Edward Kaye, MD Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.

References
  1. Nolte KW, Janecke AR, Vorgerd M, Weis J, Schroder JM. Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. Acta Neuropathol. 2008 Nov. 116(5):491-506. [Medline].

  2. Akman HO, Sampayo JN, Ross FA, et al. Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase. Pediatr Res. 2007 Oct. 62(4):499-504. [Medline].

  3. Ravenscroft G, Thompson EM, Todd EJ, et al. Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. Neuromuscul Disord. 2013 Feb. 23(2):165-9. [Medline].

  4. Raju GP, Li HC, Bali DS, et al. A case of congenital glycogen storage disease type IV with a novel GBE1 mutation. J Child Neurol. 2008 Mar. 23(3):349-52. [Medline].

  5. Mochel F, Schiffmann R, Steenweg ME, et al. Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings. Ann Neurol. 2012 Sep. 72(3):433-41. [Medline].

  6. Magoulas PL, El-Hattab AW, Roy A, Bali DS, Finegold MJ, Craigen WJ. Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review. Hum Pathol. 2012 Jun. 43(6):943-51. [Medline].

  7. Li SC, Hwu WL, Lin JL, et al. Association of the congenital neuromuscular form of glycogen storage disease type IV with a large deletion and recurrent frameshift mutation. J Child Neurol. 2012 Feb. 27(2):204-8. [Medline].

  8. Escobar LF, Wagner S, Tucker M, Wareham J. Neonatal presentation of lethal neuromuscular glycogen storage disease type IV. J Perinatol. 2012 Oct. 32(10):810-3. [Medline].

  9. Konstantinidou AE, Anninos H, Dertinger S, et al. Placental involvement in glycogen storage disease type IV. Placenta. 2008 Apr. 29(4):378-81. [Medline].

  10. Sokal EM, Van Hoof F, Alberti D, de Ville de Goyet J, de Barsy T, Otte JB. Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis. Eur J Pediatr. 1992 Mar. 151(3):200-3. [Medline].

  11. Starzl TE, Demetris AJ, Trucco M, et al. Chimerism after liver transplantation for type IV glycogen storage disease and type 1 Gaucher's disease. N Engl J Med. 1993 Mar 18. 328(11):745-9. [Medline]. [Full Text].

  12. Romano F, Stroppa P, Bravi M, et al. Favorable outcome of primary liver transplantation in children with cirrhosis and hepatocellular carcinoma. Pediatr Transplant. 2011 Sep. 15(6):573-9. [Medline].

  13. Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. 2005 Jun. 41(6):1407-32. [Medline].

  14. Escobar LF, Wagner S, Tucker M, Wareham J. Neonatal presentation of lethal neuromuscular glycogen storage disease type IV. J Perinatol. 2012 Oct. 32(10):810-3. [Medline].

  15. Akman HO, Karadimas C, Gyftodimou Y, et al. Prenatal diagnosis of glycogen storage disease type IV. Prenat Diagn. 2006 Oct. 26(10):951-5. [Medline].

  16. Bao Y, Kishnani P, Wu JY, Chen YT. Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene. J Clin Invest. 1996 Feb 15. 97(4):941-8. [Medline]. [Full Text].

  17. Brown BI, Brown DH. Branching enzyme activity of cultured amniocytes and chorionic villi: prenatal testing for type IV glycogen storage disease. Am J Hum Genet. 1989 Mar. 44(3):378-81. [Medline]. [Full Text].

  18. Bruno C, van Diggelen OP, Cassandrini D, et al. Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV). Neurology. 2004 Sep 28. 63(6):1053-8. [Medline].

  19. Burrow TA, Hopkin RJ, Bove KE, et al. Non-lethal congenital hypotonia due to glycogen storage disease type IV. Am J Med Genet A. 2006 Apr 15. 140(8):878-82. [Medline].

  20. Giuffre B, Parini R, Rizzuti T, et al. Severe neonatal onset of glycogenosis type IV: clinical and laboratory findings leading to diagnosis in two siblings. J Inherit Metab Dis. 2004. 27(5):609-19. [Medline].

  21. L'hermine-Coulomb A, Beuzen F, Bouvier R, et al. Fetal type IV glycogen storage disease: clinical, enzymatic, and genetic data of a pure muscular form with variable and early antenatal manifestations in the same family. Am J Med Genet A. 2005 Dec 1. 139A(2):118-22. [Medline].

  22. Lossos A, Meiner Z, Barash V, et al. Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene. Ann Neurol. 1998 Dec. 44(6):867-72. [Medline].

  23. Massa R, Bruno C, Martorana A, de Stefano N, van Diggelen OP, Federico A. Adult polyglucosan body disease: proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene. Muscle Nerve. 2008 Apr. 37(4):530-6. [Medline].

  24. McConkie-Rosell A, Wilson C, Piccoli DA, et al. Clinical and laboratory findings in four patients with the non-progressive hepatic form of type IV glycogen storage disease. J Inherit Metab Dis. 1996. 19(1):51-8. [Medline].

  25. Nambu M, Kawabe K, Fukuda T, et al. A neonatal form of glycogen storage disease type IV. Neurology. 2003 Aug 12. 61(3):392-4. [Medline].

  26. Nase S, Kunze KP, Sigmund M, Schroeder JM, Shin Y, Hanrath P. A new variant of type IV glycogenosis with primary cardiac manifestation and complete branching enzyme deficiency. In vivo detection by heart muscle biopsy. Eur Heart J. 1995 Nov. 16(11):1698-704. [Medline].

  27. Selby R, Starzl TE, Yunis E, et al. Liver transplantation for type I and type IV glycogen storage disease. Eur J Pediatr. 1993. 152 Suppl 1:S71-6. [Medline]. [Full Text].

  28. Servidei S, Riepe RE, Langston C, et al. Severe cardiopathy in branching enzyme deficiency. J Pediatr. 1987 Jul. 111(1):51-6. [Medline].

  29. Shen J, Liu HM, McConkie-Rosell A, Chen YT. Prenatal diagnosis of glycogen storage disease type IV using PCR-based DNA mutation analysis. Prenat Diagn. 1999 Sep. 19(9):837-9. [Medline].

 
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Liver section from a patient with glycogen-storage disease type IV (GSD IV) stained with hematoxylin and eosin. Characteristic findings include distorted hepatic architecture with diffuse interstitial fibrosis and wide fibrous septa surrounding micronodular areas of parenchyma. Hepatocytes are typically enlarged 2-fold to 3-fold, with faintly stained basophilic cytoplasmic inclusions.
Liver section from a patient with glycogen-storage disease type IV (GSD IV) stained with periodic acid-Schiff (PAS) after diastase treatment. Coarsely clumped material cytoplasmic material representing the accumulated abnormal glycogen is resistant to diastase treatment and is readily stained with PAS.
 
 
 
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