eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Glycogen-Storage Disease Type VI: Differential Diagnoses & Workup

Author: Lynne Ierardi-Curto, MD, PhD, Medical Geneticist, Laboratory Corporation of America (LabCorp), Northeast Division, Genetics Services
Contributor Information and Disclosures

Updated: Aug 4, 2008

Differential Diagnoses

Fructose 1,6-Diphosphatase Deficiency
Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)
Glycogen-Storage Disease Type 0
Glycogen-Storage Disease Type I
Glycogen-Storage Disease Type II
Glycogen-Storage Disease Type III

Workup

Laboratory Studies

The extent and severity of biochemical abnormalities vary in affected children.

  • Blood glucose: After a short fast (3-5 h), mild hypoglycemia may develop in younger patients.
  • Urine ketones, serum ketone bodies: Levels of urine ketones and serum ketone bodies (eg, acetoacetate, beta-hydroxybutyrate) may be elevated during a short fast and are proportional to the degree of fasting.
  • Lipid profile: Mild hyperlipidemia may be present, with serum cholesterol elevations higher than serum triglycerides.
  • Serum transaminases: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels may be mildly elevated. Other liver function test findings are usually normal, unless cirrhosis is present.
  • Patients with proximal renal tubule acidosis may have increased urine pH levels with abnormal levels of calcium, phosphate, and amino acids and decreased blood pH levels with a normal anion gap.

Imaging Studies

  • Liver volume quantitation may be performed using abdominal MRI or CT scanning.

Other Tests

  • Evaluation of a patient with suspected glycogen-storage disease type VI (GSD VI) requires monitored assessment of fasting adaptation in an inpatient setting. After 3-5 hours of fasting, patients with GSD VI typically exhibit hypoglycemia with a normal serum lactic acid level. This same pattern also occurs in patients with glycogen-storage disease type 0 (GSD 0) and glycogen-storage disease type III (GSD III) and in patients with hereditary fructose intolerance (HFI). Patients with HFI can be identified by development of hypoglycemia and increased lactic acid after oral fructose loading.
  • A fasted glucagon challenge may further narrow the field of diagnostic possibilities. Patients with GSD VI may have a normal hyperglycemic response without change in lactic acid after glucagon administration, although results may be inconclusive.
  • Molecular diagnostic testing for a specific mutation in the PYGL gene may be used to identify carriers and affected children in the Mennonite population.

Procedures

  • Definitive diagnosis of GSD VI requires a liver biopsy and enzyme assay. Histological examination and determination of glycogen content may also be performed.
  • An enzyme assay can be performed in more easily obtainable cells, including RBCs and WBCs. However, due to the presence of isoenzymes, the presence of normal enzyme activity in these cells does not exclude the possibility of isolated hepatic involvement in an affected patient.

Histologic Findings

  • Histological analysis of the liver typically reveals glycogen-distended hepatocytes.
  • The accumulated glycogen (ie, alpha particles, rosette form) appears frayed or burst and is less compact than the glycogen present in glycogen-storage disease types I or III.
  • Interlobular fibrous septa and low-grade inflammatory changes may be seen.
  • Liver glycogen content may also be increased as much as 4-fold, although muscle glycogen remains normal in structure and quantity.

More on Glycogen-Storage Disease Type VI

Overview: Glycogen-Storage Disease Type VI
Differential Diagnoses & Workup: Glycogen-Storage Disease Type VI
Treatment & Medication: Glycogen-Storage Disease Type VI
Follow-up: Glycogen-Storage Disease Type VI
References
[ CLOSE WINDOW ]

References

  1. Chang S, Rosenberg MJ, Morton H. Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI. Hum Mol Genet. May 1998;7(5):865-70. [Medline].

  2. Burwinkel B, Rootwelt T, Kvittingen EA. Severe phenotype of phosphorylase kinase-deficient liver glycogenosis with mutations in the PHKG2 gene. Pediatr Res. 2003;54(6):834-839. [Medline].

  3. Burwinkel B, Amat L, Gray RG. Variability of biochemical and clinical phenotype in X-linked liver glycogenosis with mutations in the phosphorylase kinase PHKA2 gene. Hum Genet. Apr 1998;102(4):423-9. [Medline].

  4. Bashan N, Iancu TC, Lerner A. Glycogenosis due to liver and muscle phosphorylase kinase deficiency. Pediatr Res. Apr 1981;15(4 Pt 1):299-303. [Medline].

  5. Beauchamp NJ, Taybert J, Champion MP et al. High frequency of missense mutations in glycogen storage disease type VI. J Inherit Metab Dis. Oct 2007;30:722-734. [Medline].

  6. Burwinkel B, Bakker HD, Herschkovitz E. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. Apr 1998;62(4):785-91. [Medline].

  7. Burwinkel B, Bakker HD, Herschkovitz E, et al. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet. Apr 1998;62(4):785-91. [Medline].

  8. Chen Y-T, Burchell A. Glycogen storage diseases. In: The Metabolic and Molecular Bases of Inherited Disease. Vol 1. 1995:935-65.

  9. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen storage diseases. J Am Diet Assoc. Dec 1993;93(12):1423-30. [Medline].

  10. Hendrickx J, Bosshard NU, Willems P. Clinical, biochemical and molecular findings in a patient with X-linked liver glycogenosis followed for 40 years. Eur J Pediatr. Nov 1998;157(11):919-23. [Medline].

  11. Hendrickx J, Lee P, Keating JP. Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type I and II. Am J Hum Genet. Jun 1999;64(6):1541-9. [Medline].

  12. Kotb MA, Abdallah HK, Kotb A. Liver glycogenoses: are they a possible cause of polyneuropathy? A cross-sectional study. J Trop Pediatr. Aug 2004;50(4):196-202. [Medline].

  13. Newgard CB, Fletterick RJ, Anderson LA. The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14. Am J Hum Genet. Apr 1987;40(4):351-64. [Medline].

  14. Ozen H. Glycogen storage diseases: new perspectives. World J Gastroenterol. May 2007;13:2541-2553. [Medline].

  15. Tang NL, Hui J, Young E, et al. A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity. Mol Genet Metab. Jun 2003;79(2):142-5. [Medline].

  16. Willems PJ, Gerver WJ, Berger R. The natural history of liver glycogenosis due to phosphorylase kinase deficiency: a longitudinal study of 41 patients. Eur J Pediatr. Jan 1990;149(4):268-71. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

glycogen storage disease type VI, Hers disease, Hers' disease, GSD, GSD VI, glycogenosis, liver phosphorylase deficiency, glycogen phosphorylase, liver phosphorylase, hepatic phosphorylase kinase, X-linked liver glycogenosis, type 6 glycogenosis, hepatophosphorylase deficiency glycogenosis, hypoglycemia, hyperketosis, growth retardation, hepatomegaly, hyperlacticacidemia, hyperuricemia, hyperlipidemia, renal tubule acidosis, phosphorylase kinase deficiency, severe cardiomyopathy, short stature

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Lynne Ierardi-Curto, MD, PhD, Medical Geneticist, Laboratory Corporation of America (LabCorp), Northeast Division, Genetics Services
Disclosure: Nothing to disclose.

Medical Editor

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, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Hagop Youssoufian, MD, MSc, Vice President of Clinical Research, ImClone Systems Incorporated
Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.